Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triti...The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triticina(Pt).However,the molecular mechanism of its interaction with a Pt effector is not clear.We found that Pt effector Pt-1234 interacts with TaNAC069 to subvert host immunity during Pt infection.Quantitative real-time PCR analysis showed that expression of Pt-1234 was significantly upregulated during the early stage of Pt infection.Protein-mediated cell death assays in wheat showed that the Pt-1234 protein was unable to induce cell death in wheat near-isogenic lines carrying different leaf rust resistance genes,whereas it suppressed BAX-induced cell death in leaves of Nicotiana benthamiana.Silencing of Pt-1234 by host-induced gene silencing(HIGS)significantly reduced the virulence of Pt in the susceptible wheat variety Thatcher.The C subdomain of TaNAC069 was responsible for its interaction with Pt-1234,and the E subdomain was required for TaNAC069-mediated defense responses to Pt in planta.These findings indicate that Pt utilizes Pt-1234 to interact with wheat transcription factor TaNAC069 through its C subdomain,thereby modulating wheat immunity.展开更多
Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomat...Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomato fruit yield.It is necessary to identify transcription factors(TFs)and target genes involved in heat stress response(HSR)signaling cascades in tomato flower buds to improve tomato plant thermotolerance.In this study,we profiled genes expressed in three developmental stages of tomato flower buds.Red and turquoise modules for heat stress(HS)were identified through gene co-expression network analysis,and the genes within these modules were enriched in HS-related pathways.By focusing on the TFs in the two modules,we identified several novel HSR-related TFs,including SlWRKY75,SlMYB117,and SlNAM.Furthermore,homology analysis illustrated a conserved signaling cascade in tomato.Lastly,we identified and experimentally validated four HSF-regulated genes,namely SlGrpE,SlERDJ3A,SlTIL,and SlPOM1,that likely modulate thermotolerance in plants.These results provide a high-resolution atlas of gene expression during tomato flower bud development under HS conditions,which is a valuable resource for uncovering potential regulatory networks associated with the HSR in tomato.展开更多
The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple c...The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essenti...BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.展开更多
Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)...Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.展开更多
Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and hea...Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.展开更多
Anthocyanins are important pigments and nutrients in fruits.Red grape is popular because of the high anthocyanin content.Previous studies have identified VvMYBA1 and its homologs as key regulators of fruit color;howev...Anthocyanins are important pigments and nutrients in fruits.Red grape is popular because of the high anthocyanin content.Previous studies have identified VvMYBA1 and its homologs as key regulators of fruit color;however,other transcription factors(TFs)that contribute to fruit color remain poorly understood.The present study identified the R2R3-MYB TF VvMYB24,whose gene expression levels were significantly higher in red berries(L51,Vitis vinifera×Vitis labrusca L.)than in green berries(L20,V.vinifera×V.labrusca L.).Overexpression of VvMYB24 in grape calli increased anthocyanin biosynthesis by upregulating the expression of specific structural genes(VvDFR and VvUFGT).Furthermore,VvMYB24 interacted with VvMYBA1 to form a protein complex that additionally increased the expression of VvDFR and VvUFGT.In addition,light-responsive TF VvHY5 could bind to the VvMYB24 promoters to activate its transcription.Taken together,the results reveal a regulatory module,VvHY5-VvMYB24-VvMYBA1,that influences anthocyanin biosynthesis in grape.展开更多
Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized ...Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.展开更多
Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance ...Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance quality,storage,and transportation of the fruits.Here,we isolated a novel few spines mutant(fs2)from the wild-type(WT)inbred line WD1,a North China-type cucumber with high density fruit spines,by an ethyl methanesulfonate(EMS)mutagenesis treatment.Genetic analysis revealed that the phenotype of fs2 is controlled by a single recessive nuclear gene.We fine-mapped the fs2 locus using F_(2) and BC_(1) populations(1,802 and 420 individuals,respectively),which showed that the candidate gene of FS2(Csa4G652850)encodes an ARID-HMG transcription factor containing an AT-rich interaction domain(ARID)and a high mobility group box domain(HMG).One SNP(C to T)and one InDel(a 40-bp deletion)in the coding region of FS2 result in amino acid variation and premature translation termination in the fs2 mutant,respectively.FS2 was found to be highly expressed in the apical buds and young ovaries.In addition,experiments suggest that FS2 participates in the regulation of fruit spine initiation by activating the expression of the Tril gene in cucumber.This work provides not only an important reference for understanding the molecular mechanisms of fruit spine development but also an important resource for fruit appearance quality breeding in cucumber.展开更多
Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and on...Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.展开更多
Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes a...Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes and metabolic pathways.ALD is involved in various transcriptional regulatory mechanisms,including lipid metabolism disorders,inflammatory responses,autophagy,fibrogenesis,oxidative stress,fatty acid metabolism,iron metabolism,and endoplasmic reticulum stress.In the occurrence of ALD and its response to the microenvironment,various transcription factors(TFs)play important roles.Targeted therapy involving these TFs may pave a novel avenue for the treatment of ALD.Here,we summarize the molecular characteristics of TFs and their involvement in the biological and pathological processes of ALD.We further discuss the current pharmaceutical treatments targeting these TFs and their mediators.This study provides detailed and accurate regulation maps of TFs for the targeted therapy of ALD.展开更多
bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the pres...bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.展开更多
BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC ...BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC pathobiology is being increasingly recognized.AIM To investigate the role of OCT4 in pancreatic CSCs and its effect on PC cell prolif-eration,migration,drug sensitivity,and stemness maintenance.METHODS We analyzed OCT4 and CD133 expression in PC tissues and cell lines.BxPC-3 cells were used to assess the effects of OCT4 modulation on cellular behavior.Proliferation,migration,and stemness of BxPC-3 cells were evaluated,and the PI3K/AKT/mTOR pathway was examined to gain mechanistic insights.RESULTS OCT4 and CD133 were significantly overexpressed in PC tissues.OCT4 mo-dulation altered BxPC-3 cell proliferation,invasion,and stemness,with OCT4 overexpression(OV-OCT4)enhancing these properties and OCT4 interference decreasing them.OV-OCT4 activated the PI3K/AKT/mTOR pathway,which correlated with an increase in PC stem cells(PCSC).CONCLUSION OCT4 plays a crucial role in PCSCs by influencing the aggressiveness and drug resistance of PC cells,thus presenting itself as a potential therapeutic target.展开更多
BACKGROUND Transcription factor 3(TCF3)has a vital role in tumor occurrence and progression.However,the specific functions and underlying mechanisms of dysregulated TCF3 in hepatocellular carcinoma(HCC)have not been n...BACKGROUND Transcription factor 3(TCF3)has a vital role in tumor occurrence and progression.However,the specific functions and underlying mechanisms of dysregulated TCF3 in hepatocellular carcinoma(HCC)have not been not thoroughly charac-terized.Thus,we explored the roles of TCF3 in HCC.METHODS TCF3 knockdown and overexpression models were developed via lentiviral vectors in HCC cells.Transwell and in vivo metastasis experiments were per-formed to measure the effects of TCF3 on HCC cell metastasis.Then,reverse transcription-quantitative polymerase chain reaction,serial deletion,western blotting,site-directed mutagenesis,chromatin immunoprecipitation,and dual-luciferase reporter assays were done to determine the pathomechanisms.RESULTS TCF3 levels were markedly elevated in HCC samples and correlated with poor prognosis.Furthermore,overex-pression of TCF3 promoted HCC cell invasion as well as migration,while TCF3 knockdown repressed HCC cell growth.In addition,TCF3 interacted with the promoter region of matrix metalloproteinase-11(MMP11),facilitating the transcriptional activation of MMP11 mRNA,which consequently enhanced the expression of MMP11.MMP11 knockdown repressed TCF3-associated HCC cell migration and invasion,while its overex-pression attenuated the TCF3 knockdown-mediated repression of HCC growth.In human-derived HCC samples,TCF3 was positively correlated with MMP11 expression levels.CONCLUSION TCF3 was significantly upregulated in HCC.TCF3 overexpression enhanced HCC cell invasion and metastasis through transactivation of MMP11 expression.TCF3 could be a prognostic biomarker and regulator of HCC metastasis.展开更多
Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed ...Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their c...Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their crucial role in coordinating growth–defense trade-offs through transcriptional regulation of key biosynthetic and stress-response genes.Despite extensive functional characterization in model plants such as Arabidopsis thaliana,systematically evaluating the broader functional landscape of MYB TFs across diverse species and contexts remains necessary.This systematic review integrates results from 24 peer-reviewed studies sourced from Scopus and Web of Science,focusing on the functional diversity of MYB TFs,particularly in relation to abiotic stress tolerance,metabolic regulation,and plant developmental processes.Advances in genomic technologies,such as transcriptomics,genome editing,and comparative phylogenetics,have considerably enhanced our understanding of MYB-mediated regulatory mechanisms.These tools have facilitated the identification and functional characterization of MYB genes across model and non-model plant species.Key findings underscore the multifaceted roles of MYB TFs in enhancing stress resilience,modulating anthocyanin and flavonoid biosynthesis,and contributing to yield-related traits,thereby highlighting their potential applications in crop improvement and sustainable agriculture.However,critical gaps exist in understanding MYB interactions within complex regulatory networks,particularly in underrepresented plant species and ecological contexts.This review consolidates current knowledge as well as identifies research gaps and proposes future directions to advance the understanding and application of MYB TFs.The insights derived from this study underscore their transformative potential in addressing global challenges including food security and climate resilience through innovative agricultural practices.展开更多
Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has bee...Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.展开更多
Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus rem...Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus remain largely unknown.Here,we found that all six paralogs of C2H2 zinc finger transcription factor WIP DOMAIN PROTEIN 2(BnaWIP2)showed increased expression during the initial 12 hours of germination,and expression was further enhanced by salinity stress.Under NaCl treatment,knocking out all six BnaWIP2 paralogs in B.napus led to significantly reduced germination,while overexpression of BnaC06.WIP2 promoted germination.Transcriptomic analysis revealed that BnaC06.WIP2 downregulated a series of genes related to abscisic acid(ABA)biosynthesis and signaling,among which BnaA05.NCED3,BnaC04.ABI5-2,BnaA03.EM6,and BnaA05.EM6 were directly repressed by BnaC06.WIP2.Further analysis showed that in germinating seeds,BnaC06.WIP2 was induced by ABA and in turn restrained ABA production,indicating that BnaC06.WIP2 forms a negative feedback loop with ABA to promote seed germination under salinity stress in B.napus.Collectively,these results enhance our understanding of the novel function of BnaWIP2 and provide valuable genetic resources for breeding salinity-tolerant rapeseed varieties.展开更多
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
基金funded by State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2023ZZ-10)the National Natural Science Foundation of China(32172384 and 31501623)+1 种基金the Natural Science Foundation of Hebei(C2020204028)the Science and Technology Research Project of Higher Education of Hebei(ZC2023178).
文摘The NAC(NAM,ATAF1/2,and CUC2)is a defense-associated transcription factor(TF)family that positively regulates defense responses to pathogen infection.TaNAC069 positively regulates resistance in wheat to Puccinia triticina(Pt).However,the molecular mechanism of its interaction with a Pt effector is not clear.We found that Pt effector Pt-1234 interacts with TaNAC069 to subvert host immunity during Pt infection.Quantitative real-time PCR analysis showed that expression of Pt-1234 was significantly upregulated during the early stage of Pt infection.Protein-mediated cell death assays in wheat showed that the Pt-1234 protein was unable to induce cell death in wheat near-isogenic lines carrying different leaf rust resistance genes,whereas it suppressed BAX-induced cell death in leaves of Nicotiana benthamiana.Silencing of Pt-1234 by host-induced gene silencing(HIGS)significantly reduced the virulence of Pt in the susceptible wheat variety Thatcher.The C subdomain of TaNAC069 was responsible for its interaction with Pt-1234,and the E subdomain was required for TaNAC069-mediated defense responses to Pt in planta.These findings indicate that Pt utilizes Pt-1234 to interact with wheat transcription factor TaNAC069 through its C subdomain,thereby modulating wheat immunity.
基金supported by grants from the National Natural Science Foundation of China(Grant No.32072571)the 111 Project(Grant No.B17043)the Construction of Beijing Science,and Technology Innovation and Service Capacity in Top Subjects(Grant No.CEFF-PXM2019_014207_000032)。
文摘Tomato(Solanum lycopersicum)is an important fruit and vegetable crop in worldwide.The fertility of tomato reproductive organs can be dramatically decreased when ambient temperatures rise above 35°C,reducing tomato fruit yield.It is necessary to identify transcription factors(TFs)and target genes involved in heat stress response(HSR)signaling cascades in tomato flower buds to improve tomato plant thermotolerance.In this study,we profiled genes expressed in three developmental stages of tomato flower buds.Red and turquoise modules for heat stress(HS)were identified through gene co-expression network analysis,and the genes within these modules were enriched in HS-related pathways.By focusing on the TFs in the two modules,we identified several novel HSR-related TFs,including SlWRKY75,SlMYB117,and SlNAM.Furthermore,homology analysis illustrated a conserved signaling cascade in tomato.Lastly,we identified and experimentally validated four HSF-regulated genes,namely SlGrpE,SlERDJ3A,SlTIL,and SlPOM1,that likely modulate thermotolerance in plants.These results provide a high-resolution atlas of gene expression during tomato flower bud development under HS conditions,which is a valuable resource for uncovering potential regulatory networks associated with the HSR in tomato.
基金supported by Research Program for Agricultural Science and Technology Development,Republic of Korea(PJ01570601)the Fellowship Program(PJ01661001)of the National Institute of Agricultural Sciences,Republic of KoreaRural Development Administration,Republic of Korea.
文摘The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
文摘BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.
文摘Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30886).
文摘Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.
基金supported by the National Natural Science Foundation of China(Grant No.31972368)the China Agriculture Research System(Grant No.CARS-29-yc-6)+1 种基金the Major Agricultural Science Projects of Liaoning Province(Grant No.2023JH1/10200004)the Science and Technology Program of Shenyang(Grant No.23-410-2-03).
文摘Anthocyanins are important pigments and nutrients in fruits.Red grape is popular because of the high anthocyanin content.Previous studies have identified VvMYBA1 and its homologs as key regulators of fruit color;however,other transcription factors(TFs)that contribute to fruit color remain poorly understood.The present study identified the R2R3-MYB TF VvMYB24,whose gene expression levels were significantly higher in red berries(L51,Vitis vinifera×Vitis labrusca L.)than in green berries(L20,V.vinifera×V.labrusca L.).Overexpression of VvMYB24 in grape calli increased anthocyanin biosynthesis by upregulating the expression of specific structural genes(VvDFR and VvUFGT).Furthermore,VvMYB24 interacted with VvMYBA1 to form a protein complex that additionally increased the expression of VvDFR and VvUFGT.In addition,light-responsive TF VvHY5 could bind to the VvMYB24 promoters to activate its transcription.Taken together,the results reveal a regulatory module,VvHY5-VvMYB24-VvMYBA1,that influences anthocyanin biosynthesis in grape.
基金supported by the Guangdong Basic and Applied Basic Research Foundation under Grant(2023A1515011243)National Natural Science Foundation of China under Grant(82004141)+2 种基金Bao’an Traditional Chinese Medicine Development Foundation under Grant(2022KJCX-ZJZL-11)Science,Technology,and Innovation Commission of Shenzhen Municipality under Grant(JCYJ20190808160407500)Shenzhen Bao’an Traditional Chinese Medicine Hospital Research Program under Grant(BAZYY20220701).
文摘Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.
基金supported by the National Natural Science Foundation of China(31972425)the Shanghai Agriculture Applied Technology Development Program,China(2020-02-08-00-08-F0148)。
文摘Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance quality,storage,and transportation of the fruits.Here,we isolated a novel few spines mutant(fs2)from the wild-type(WT)inbred line WD1,a North China-type cucumber with high density fruit spines,by an ethyl methanesulfonate(EMS)mutagenesis treatment.Genetic analysis revealed that the phenotype of fs2 is controlled by a single recessive nuclear gene.We fine-mapped the fs2 locus using F_(2) and BC_(1) populations(1,802 and 420 individuals,respectively),which showed that the candidate gene of FS2(Csa4G652850)encodes an ARID-HMG transcription factor containing an AT-rich interaction domain(ARID)and a high mobility group box domain(HMG).One SNP(C to T)and one InDel(a 40-bp deletion)in the coding region of FS2 result in amino acid variation and premature translation termination in the fs2 mutant,respectively.FS2 was found to be highly expressed in the apical buds and young ovaries.In addition,experiments suggest that FS2 participates in the regulation of fruit spine initiation by activating the expression of the Tril gene in cucumber.This work provides not only an important reference for understanding the molecular mechanisms of fruit spine development but also an important resource for fruit appearance quality breeding in cucumber.
文摘Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.
基金supported by the National Natural Science Foundation of China(No.82160818)the Innovative Research Group Project of the National Natural Science Foundation of China(No.22JR5RA622).
文摘Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes and metabolic pathways.ALD is involved in various transcriptional regulatory mechanisms,including lipid metabolism disorders,inflammatory responses,autophagy,fibrogenesis,oxidative stress,fatty acid metabolism,iron metabolism,and endoplasmic reticulum stress.In the occurrence of ALD and its response to the microenvironment,various transcription factors(TFs)play important roles.Targeted therapy involving these TFs may pave a novel avenue for the treatment of ALD.Here,we summarize the molecular characteristics of TFs and their involvement in the biological and pathological processes of ALD.We further discuss the current pharmaceutical treatments targeting these TFs and their mediators.This study provides detailed and accurate regulation maps of TFs for the targeted therapy of ALD.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20242007)the Natural Science Foundation of China(32271916)the Jiangsu Agricultural Science and Technology Innovation Fund[CX(24)3048].
文摘bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.
基金Supported by Inner Mongolia Natural Science Foundation and the 3rd Affiliated of Inner Medical University,No.2021MS08067.
文摘BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC pathobiology is being increasingly recognized.AIM To investigate the role of OCT4 in pancreatic CSCs and its effect on PC cell prolif-eration,migration,drug sensitivity,and stemness maintenance.METHODS We analyzed OCT4 and CD133 expression in PC tissues and cell lines.BxPC-3 cells were used to assess the effects of OCT4 modulation on cellular behavior.Proliferation,migration,and stemness of BxPC-3 cells were evaluated,and the PI3K/AKT/mTOR pathway was examined to gain mechanistic insights.RESULTS OCT4 and CD133 were significantly overexpressed in PC tissues.OCT4 mo-dulation altered BxPC-3 cell proliferation,invasion,and stemness,with OCT4 overexpression(OV-OCT4)enhancing these properties and OCT4 interference decreasing them.OV-OCT4 activated the PI3K/AKT/mTOR pathway,which correlated with an increase in PC stem cells(PCSC).CONCLUSION OCT4 plays a crucial role in PCSCs by influencing the aggressiveness and drug resistance of PC cells,thus presenting itself as a potential therapeutic target.
基金Supported by Sichuan Clinical Key Specialty,No.2017JQ0039 and No.2017KZ0028.
文摘BACKGROUND Transcription factor 3(TCF3)has a vital role in tumor occurrence and progression.However,the specific functions and underlying mechanisms of dysregulated TCF3 in hepatocellular carcinoma(HCC)have not been not thoroughly charac-terized.Thus,we explored the roles of TCF3 in HCC.METHODS TCF3 knockdown and overexpression models were developed via lentiviral vectors in HCC cells.Transwell and in vivo metastasis experiments were per-formed to measure the effects of TCF3 on HCC cell metastasis.Then,reverse transcription-quantitative polymerase chain reaction,serial deletion,western blotting,site-directed mutagenesis,chromatin immunoprecipitation,and dual-luciferase reporter assays were done to determine the pathomechanisms.RESULTS TCF3 levels were markedly elevated in HCC samples and correlated with poor prognosis.Furthermore,overex-pression of TCF3 promoted HCC cell invasion as well as migration,while TCF3 knockdown repressed HCC cell growth.In addition,TCF3 interacted with the promoter region of matrix metalloproteinase-11(MMP11),facilitating the transcriptional activation of MMP11 mRNA,which consequently enhanced the expression of MMP11.MMP11 knockdown repressed TCF3-associated HCC cell migration and invasion,while its overex-pression attenuated the TCF3 knockdown-mediated repression of HCC growth.In human-derived HCC samples,TCF3 was positively correlated with MMP11 expression levels.CONCLUSION TCF3 was significantly upregulated in HCC.TCF3 overexpression enhanced HCC cell invasion and metastasis through transactivation of MMP11 expression.TCF3 could be a prognostic biomarker and regulator of HCC metastasis.
文摘Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
基金funded by the Fundamental Research Grant Scheme(Grant No.FRGS/1/2023/STG03/UM/02/2)Universiti Malaya RU Grant(RU002-2025B).
文摘Myeloblastosis(MYB)transcription factors(TFs)are evolutionarily conserved regulatory proteins that are crucial for plantgrowth,development,secondarymetabolism,andstress adaptation.Recent studieshavehighlighted their crucial role in coordinating growth–defense trade-offs through transcriptional regulation of key biosynthetic and stress-response genes.Despite extensive functional characterization in model plants such as Arabidopsis thaliana,systematically evaluating the broader functional landscape of MYB TFs across diverse species and contexts remains necessary.This systematic review integrates results from 24 peer-reviewed studies sourced from Scopus and Web of Science,focusing on the functional diversity of MYB TFs,particularly in relation to abiotic stress tolerance,metabolic regulation,and plant developmental processes.Advances in genomic technologies,such as transcriptomics,genome editing,and comparative phylogenetics,have considerably enhanced our understanding of MYB-mediated regulatory mechanisms.These tools have facilitated the identification and functional characterization of MYB genes across model and non-model plant species.Key findings underscore the multifaceted roles of MYB TFs in enhancing stress resilience,modulating anthocyanin and flavonoid biosynthesis,and contributing to yield-related traits,thereby highlighting their potential applications in crop improvement and sustainable agriculture.However,critical gaps exist in understanding MYB interactions within complex regulatory networks,particularly in underrepresented plant species and ecological contexts.This review consolidates current knowledge as well as identifies research gaps and proposes future directions to advance the understanding and application of MYB TFs.The insights derived from this study underscore their transformative potential in addressing global challenges including food security and climate resilience through innovative agricultural practices.
基金supported by the National Natural Science Foundation of China[grant numbers 32271914 and 32301660]the Quality Engineering Project of Anhui Provincial Department of Education[grant number 2023zygzts007].
文摘Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.
基金supported by the Biological Breeding-National Science and Technology Major Project(2022ZD04010)Scientific and Technological Innovation Team of Shaanxi Province(2024RS-CXTD-69)+1 种基金Key Research and Development Program of Shaanxi Province(2021LLRH-07)a grant from the Yang Ling Seed Industry Innovation Center(K3031122024).
文摘Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus remain largely unknown.Here,we found that all six paralogs of C2H2 zinc finger transcription factor WIP DOMAIN PROTEIN 2(BnaWIP2)showed increased expression during the initial 12 hours of germination,and expression was further enhanced by salinity stress.Under NaCl treatment,knocking out all six BnaWIP2 paralogs in B.napus led to significantly reduced germination,while overexpression of BnaC06.WIP2 promoted germination.Transcriptomic analysis revealed that BnaC06.WIP2 downregulated a series of genes related to abscisic acid(ABA)biosynthesis and signaling,among which BnaA05.NCED3,BnaC04.ABI5-2,BnaA03.EM6,and BnaA05.EM6 were directly repressed by BnaC06.WIP2.Further analysis showed that in germinating seeds,BnaC06.WIP2 was induced by ABA and in turn restrained ABA production,indicating that BnaC06.WIP2 forms a negative feedback loop with ABA to promote seed germination under salinity stress in B.napus.Collectively,these results enhance our understanding of the novel function of BnaWIP2 and provide valuable genetic resources for breeding salinity-tolerant rapeseed varieties.
