Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.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
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
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
BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM...BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.展开更多
POU transcription factor OCT4 not only plays an essential role in maintaining the pluripotent and self-renewing state of embryonic stem （ES） cells but also acts as a cell fate determinant through a gene dosage effec...POU transcription factor OCT4 not only plays an essential role in maintaining the pluripotent and self-renewing state of embryonic stem （ES） cells but also acts as a cell fate determinant through a gene dosage effect. However, the molecular mechanisms that control the intracellular OCT4 protein level remain elusive. Here, we report that human WWP2, an E3 ubiquitin （Ub）-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo. We first demonstrated that endogenous OCT4 in hu- man ES cells can be post-translationally modified by Ub. Furthermore, we found that WWP2 promoted degradation of OCT4 through the 26S proteasome in a dosage-dependent manner, and the active site cysteine residue of WWP2 was required for both its enzymatic activity and proteolytic effect on OCT4. Remarkably, our data show that the en- dogenous OCT4 protein level was significantly elevated when WWP2 expression was downregulated by specific RNA interference （RNAi）, suggesting that WWP2 is an important regulator for maintaining a proper OCT4 protein level in human ES cells. Moreover, northern blot analysis showed that the WWP2 transcript was widely present in diverse human tissues/organs and highly expressed in undifferentiated human ES cells. However, its expression level was quickly decreased after human ES cells differentiated, indicating that WWP2 expression might be developmentally regulated. Our findings demonstrate that WWP2 is an important regulator of the OCT4 protein level in human ES cells.展开更多
Camptotheca acuminata produces camptothecin(CPT),a monoterpene indole alkaloid(MIA)that is widely used in the treatment of lung,colorectal,cervical,and ovarian cancers.Its biosynthesis pathway has attracted significan...Camptotheca acuminata produces camptothecin(CPT),a monoterpene indole alkaloid(MIA)that is widely used in the treatment of lung,colorectal,cervical,and ovarian cancers.Its biosynthesis pathway has attracted significant attention,but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor(AP2/ERF)transcription factors(TFs)remains unclear.In this study,a systematic analysis of the AP2/ERF TFs family in C.acuminata was performed,including phylogeny,gene structure,conserved motifs,and gene expression profiles in different tissues and organs(immature bark,cotyledons,young flower,immature fruit,mature fruit,mature leaf,roots,upper stem,and lower stem)of C.acuminata.A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies,including AP2(26 genes),DREB(61 genes),ERF(92 genes),RAV(18 genes),and Soloist(one gene).The combination of gene expression patterns in different C.acuminata tissues and organs,the phylogenetic tree,the co-expression analysis with biosynthetic genes,and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C.acuminata might be involved in CPT synthesis regulation,which exhibit relatively high expression levels in the upper stem or immature bark.Among these,four genes(Cac AP2/ERF123,Cac AP2/ERF125,Cac AP2/ERF126,and Cac AP2/ERF127)belong to the ERF–B2 subgroup;two genes(Cac AP2/ERF149 and Cac AP2/ERF152)belong to the ERF–B3 subgroup;and two more genes(Cac AP2/ERF095 and Cac AP2/ERF096)belong to the DREB–A6 subgroup.These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C.acuminata.展开更多
Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both...Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both in ascomycete and basidiomycete fungi.We found that ZnFTFs were widely distributed in these fungal species,but there was more expansion of the ZnFTF class in Ascomycota than Basidiomycota.We identified 40 ZnFTFs in Ustilaginoidea virens,and demonstrated the involvement of UvZnFTF1 in vegetative growth,conidiation,pigment biosynthesis and pathogenicity.RNA-Seq analysis suggested that UvZnFTF1 may regulate different nutrient metabolism pathways,the production of secondary metabolites,and the expression of pathogen-host interaction genes and secreted protein-encodi ng genes.Analysis of the distributi on of differe nt fungal TFs in U.virens further dem on strated that UvZnFTFs make up a large TF family and may play essential biological roles in U.virens.展开更多
Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related ...Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related genes responsible for seed specific triacylglycerols (TAGs) storage in oil plants. B3 type transcription factors, such as ABI3 and FUS3, are known to be involved in seed development, such as seed storage protein synthesis and maturation. Based on the recent whole genome sequence data of castor bean (Ricinus communis L.), putative WRI1 homologs (RcWRI1, RcWRI2) specifically expressed in castor bean seed have been identified by comparing organ specific expression profiles among seed development-related transcription factors, seed storage specific genes (Ricin, RcOleosin) and a set of FAS genes including genes for sucrose synthase (RcSUS2), biotin carboxyl carrier protein (a subunit of acetyl-CoA carboxylase, RcBCCP2) and ketoacyl-acyl carrier protein synthase (RcKAS1). Immunoreactive signals with WRI1, FUS3 and ABI5-related polypeptides were also detected in seed specifically, consistent with the expression profiles of seed development-related genes. The WRI1 binding consensus sites, [CnTnG](n)(7)[CG], designated as the AW-box, were found at the promoter region of RcBCCP2 and RcKAS1. Thus, RcWRI1 possibly play a pivotal role in seed specific TAGs storage during seed development by directly activating FAS -related genes.展开更多
To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rat...To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rats subjected to hypoxia. Immunohistochemistry demonstrated that Olig2 was expressed throughout the nuclei in the brain, and expression increased at 3 days following hypoxia and was higher than levels at 7 days following Ad5-Oligl transfection. Western blot revealed that Oligl and Olig2 expression increased in Oligl-transfected brain cells 3 days after hypoxia, but Oligl and Olig2 expression decreased at 7 days. These results indicate that Oligl overexpression enhances Olig2 expression in brain tissues of hypoxia rats.展开更多
Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified ...Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified a gene(named GaPC) controlling petal coloration in Gossypium arboreum and following a heritable recessive epistatic genetic model. Petal coloration is controlled by a single dominant gene,GaPC. A loss-of-function mutation of GaPC leads to a recessive gene Gapc that masks the phenotype of other color genes and shows recessive epistatic interactions. Map-based cloning showed that GaPC encodes an R2R3-MYB transcription factor. A 4814-bp long terminal repeat retrotransposon insertion at the second exon led to GaPC loss of function and disabled petal coloration. GaPC controlled petal coloration by regulating the anthocyanin and flavone biosynthesis pathways. Expression of core genes in the phenylpropanoid and anthocyanin pathways was higher in colored than in white petals. Petal color was conferred by flavonoids and anthocyanins, with red and yellow petals rich in anthocyanin and flavonol glycosides, respectively. This study provides new insight on molecular mechanism of recessive epistasis,also has potential breeding value by engineering GaPC to develop colored petals or fibers for multifunctional utilization of cotton.展开更多
BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the ...BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.展开更多
BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importanc...BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.展开更多
Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto inves...Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto investigate the expression of activated EGFR andE2F in CA patients. Results: The expression of activated EGFR on themembrane of epithelial cells in CA lesions was sig-nificantly greater compared to expression levers inthe control group (P<0.01). Moreover, the co-expres-sion of activated EGFR and E2F was significantly in-creased compared to the control group (P<0.01). Conclusion: Our observations suggest that the in-crease in activated EGFR expression may stimulatehyperplasia in CA patients through the activation oftranscription factor E2F.展开更多
Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Meth...Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Methods： Expression level of PBX2 was immunohistochemically examined in 66 GSCC subjects （30 men and 36 women） with ages ranging from 42 to 85 （median 64.5） years, in which staining intensity in tumor cells was categorized as either weaker （level 1 ） or equal to/stronger （level 2） than that in the endothelial cells. Results： PBX2 expression is correlated with valosin-containing protein （VCP） expression. Univariate and multivariate analyses revealed a high level of PBX2 expression to be a poor prognosticator for disease-free survival （DFS） and overall survival （OS）, and PBX2 expression was an independent prognostic factor for both DFS and OS in GSCC. Conclusions： PBX2 expression level in GSCC is proqnostic. PBX2 may be a useful marker to identify the potential for progression in GSCC.展开更多
BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify ...BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.展开更多
BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its ro...BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.展开更多
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
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.
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.
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 Sailing Program of Naval Medical University,Program of Shanghai Hongkou District Health Commission,No.2202-27Special Funds for Activating Scientific Research of Shanghai Fourth People’s Hospital,No.sykyqd05801.
文摘BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.
基金Acknowledgments We are grateful to Dr DA Melton （Harvard University） for shar- ing his human ES cells with us. The study was supported by grants from the National High Technology Research and Development Program of China （2006CB943900）, the National Natural Science Foundation of China （General Program, 30500088）, the Shang- hai Jiao Tong University School of Medicine, and the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. The study was also supported by the Shanghai Leading Academic Deciline Project （S30201）.
文摘POU transcription factor OCT4 not only plays an essential role in maintaining the pluripotent and self-renewing state of embryonic stem （ES） cells but also acts as a cell fate determinant through a gene dosage effect. However, the molecular mechanisms that control the intracellular OCT4 protein level remain elusive. Here, we report that human WWP2, an E3 ubiquitin （Ub）-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo. We first demonstrated that endogenous OCT4 in hu- man ES cells can be post-translationally modified by Ub. Furthermore, we found that WWP2 promoted degradation of OCT4 through the 26S proteasome in a dosage-dependent manner, and the active site cysteine residue of WWP2 was required for both its enzymatic activity and proteolytic effect on OCT4. Remarkably, our data show that the en- dogenous OCT4 protein level was significantly elevated when WWP2 expression was downregulated by specific RNA interference （RNAi）, suggesting that WWP2 is an important regulator for maintaining a proper OCT4 protein level in human ES cells. Moreover, northern blot analysis showed that the WWP2 transcript was widely present in diverse human tissues/organs and highly expressed in undifferentiated human ES cells. However, its expression level was quickly decreased after human ES cells differentiated, indicating that WWP2 expression might be developmentally regulated. Our findings demonstrate that WWP2 is an important regulator of the OCT4 protein level in human ES cells.
基金supported by the National Key R&D Program of China(No.2019YFC1711100)the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2016-I2M-3-016)。
文摘Camptotheca acuminata produces camptothecin(CPT),a monoterpene indole alkaloid(MIA)that is widely used in the treatment of lung,colorectal,cervical,and ovarian cancers.Its biosynthesis pathway has attracted significant attention,but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor(AP2/ERF)transcription factors(TFs)remains unclear.In this study,a systematic analysis of the AP2/ERF TFs family in C.acuminata was performed,including phylogeny,gene structure,conserved motifs,and gene expression profiles in different tissues and organs(immature bark,cotyledons,young flower,immature fruit,mature fruit,mature leaf,roots,upper stem,and lower stem)of C.acuminata.A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies,including AP2(26 genes),DREB(61 genes),ERF(92 genes),RAV(18 genes),and Soloist(one gene).The combination of gene expression patterns in different C.acuminata tissues and organs,the phylogenetic tree,the co-expression analysis with biosynthetic genes,and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C.acuminata might be involved in CPT synthesis regulation,which exhibit relatively high expression levels in the upper stem or immature bark.Among these,four genes(Cac AP2/ERF123,Cac AP2/ERF125,Cac AP2/ERF126,and Cac AP2/ERF127)belong to the ERF–B2 subgroup;two genes(Cac AP2/ERF149 and Cac AP2/ERF152)belong to the ERF–B3 subgroup;and two more genes(Cac AP2/ERF095 and Cac AP2/ERF096)belong to the DREB–A6 subgroup.These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C.acuminata.
基金supported by the National Natural Science Foundation of China(Grant No.31601593)the Young Elite Scientist Sponsorship of China Association for Science and Technology(Grant No.YESS20170108)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20160588).
文摘Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both in ascomycete and basidiomycete fungi.We found that ZnFTFs were widely distributed in these fungal species,but there was more expansion of the ZnFTF class in Ascomycota than Basidiomycota.We identified 40 ZnFTFs in Ustilaginoidea virens,and demonstrated the involvement of UvZnFTF1 in vegetative growth,conidiation,pigment biosynthesis and pathogenicity.RNA-Seq analysis suggested that UvZnFTF1 may regulate different nutrient metabolism pathways,the production of secondary metabolites,and the expression of pathogen-host interaction genes and secreted protein-encodi ng genes.Analysis of the distributi on of differe nt fungal TFs in U.virens further dem on strated that UvZnFTFs make up a large TF family and may play essential biological roles in U.virens.
文摘Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related genes responsible for seed specific triacylglycerols (TAGs) storage in oil plants. B3 type transcription factors, such as ABI3 and FUS3, are known to be involved in seed development, such as seed storage protein synthesis and maturation. Based on the recent whole genome sequence data of castor bean (Ricinus communis L.), putative WRI1 homologs (RcWRI1, RcWRI2) specifically expressed in castor bean seed have been identified by comparing organ specific expression profiles among seed development-related transcription factors, seed storage specific genes (Ricin, RcOleosin) and a set of FAS genes including genes for sucrose synthase (RcSUS2), biotin carboxyl carrier protein (a subunit of acetyl-CoA carboxylase, RcBCCP2) and ketoacyl-acyl carrier protein synthase (RcKAS1). Immunoreactive signals with WRI1, FUS3 and ABI5-related polypeptides were also detected in seed specifically, consistent with the expression profiles of seed development-related genes. The WRI1 binding consensus sites, [CnTnG](n)(7)[CG], designated as the AW-box, were found at the promoter region of RcBCCP2 and RcKAS1. Thus, RcWRI1 possibly play a pivotal role in seed specific TAGs storage during seed development by directly activating FAS -related genes.
基金the National Natural Science Foundation of China, No. 30872778/C1704the Natural Science Foundation of Beijing, No. 7072023+1 种基金the Clinical Basic Cooperation Foundation of Capital Medical University, No. 2009jl18the Clinical Basic Cooperation Foundation of Capital Medical University, No.11JL-L03
文摘To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rats subjected to hypoxia. Immunohistochemistry demonstrated that Olig2 was expressed throughout the nuclei in the brain, and expression increased at 3 days following hypoxia and was higher than levels at 7 days following Ad5-Oligl transfection. Western blot revealed that Oligl and Olig2 expression increased in Oligl-transfected brain cells 3 days after hypoxia, but Oligl and Olig2 expression decreased at 7 days. These results indicate that Oligl overexpression enhances Olig2 expression in brain tissues of hypoxia rats.
基金supported by the Fundamental Research Funds for the Central Universities(KYZZ2022003)Jiangsu Collaborative Innovation Center for Modern Crop Production project (No.10)。
文摘Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified a gene(named GaPC) controlling petal coloration in Gossypium arboreum and following a heritable recessive epistatic genetic model. Petal coloration is controlled by a single dominant gene,GaPC. A loss-of-function mutation of GaPC leads to a recessive gene Gapc that masks the phenotype of other color genes and shows recessive epistatic interactions. Map-based cloning showed that GaPC encodes an R2R3-MYB transcription factor. A 4814-bp long terminal repeat retrotransposon insertion at the second exon led to GaPC loss of function and disabled petal coloration. GaPC controlled petal coloration by regulating the anthocyanin and flavone biosynthesis pathways. Expression of core genes in the phenylpropanoid and anthocyanin pathways was higher in colored than in white petals. Petal color was conferred by flavonoids and anthocyanins, with red and yellow petals rich in anthocyanin and flavonol glycosides, respectively. This study provides new insight on molecular mechanism of recessive epistasis,also has potential breeding value by engineering GaPC to develop colored petals or fibers for multifunctional utilization of cotton.
文摘BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.
基金江西省自然科学基金项目(编号:20202BAB206075)江西省教育厅科技项目(编号:GJJ201202)江西中医药大学中西医结合一级学科平台(Discipline of Chinese and Western Integrative Medicine,Jiangxi University of Chinese Medicine)。
基金Supported by Key Research and Development Program of Shandong Province,No.2021CXGC011101Special Fund for Taishan Scholars Project,No.tsqn202211324+2 种基金National Natural Science Foundation of China,No.81900669Natural Science Foundation of Shandong Province,China,No.ZR2018PH007the Multidisciplinary Innovation Center for Nephrology of the Second Hospital of Shandong University.
文摘BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.
文摘Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto investigate the expression of activated EGFR andE2F in CA patients. Results: The expression of activated EGFR on themembrane of epithelial cells in CA lesions was sig-nificantly greater compared to expression levers inthe control group (P<0.01). Moreover, the co-expres-sion of activated EGFR and E2F was significantly in-creased compared to the control group (P<0.01). Conclusion: Our observations suggest that the in-crease in activated EGFR expression may stimulatehyperplasia in CA patients through the activation oftranscription factor E2F.
基金Project (No. 30801382) supported by the National Natural Science Foundation of China
文摘Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Methods： Expression level of PBX2 was immunohistochemically examined in 66 GSCC subjects （30 men and 36 women） with ages ranging from 42 to 85 （median 64.5） years, in which staining intensity in tumor cells was categorized as either weaker （level 1 ） or equal to/stronger （level 2） than that in the endothelial cells. Results： PBX2 expression is correlated with valosin-containing protein （VCP） expression. Univariate and multivariate analyses revealed a high level of PBX2 expression to be a poor prognosticator for disease-free survival （DFS） and overall survival （OS）, and PBX2 expression was an independent prognostic factor for both DFS and OS in GSCC. Conclusions： PBX2 expression level in GSCC is proqnostic. PBX2 may be a useful marker to identify the potential for progression in GSCC.
文摘BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.
文摘BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.
