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Foxg1 and companions:Not only transcription factors
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作者 Antonello Mallamaci Osvaldo Artimagnella Gabriele Liuzzi 《Neural Regeneration Research》 2026年第8期3426-3438,共13页
Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and pos... Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and post-transcriptional steps of gene expression.Then,after further analysis of the literature,we report evidence that,not strictly limited to neurodevelopmental effectors,such pleiotropy also applies to other transcription factors,involved in physiology and homeostasis.Furthermore,through the systematic analysis of a major public protein-protein interaction database,we gather strong evidence that the involvement of“canonical”transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon,characterizing hundreds of effectors.Finally,we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario. 展开更多
关键词 BioGrid co-transcriptional transfer genetic pleiotropy neuronal plasticity POLYADENYLATION protein biosynthesis SPLICING transcription factors triplosensitivity
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Transcription factor ZbERF6-ZbbHLH2 complex enhances monoterpenoid synthesis in Zanthoxylum bungeanum by synergistically activating the expression of ZbIDI 被引量:1
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作者 Jie Zhang Nuan Han +3 位作者 Ziyi Wang Bobo Li Cheng Wang Dongmei Wang 《The Crop Journal》 2026年第1期271-284,共14页
Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research a... Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research area.However,the transcriptional regulatory mechanisms underlying monoterpenoid synthesis in Z.bungeanum remain unclear,hindering these breeding efforts.In this study,RNA sequencing,gas chromatography–mass spectrometry,and other molecular biology techniques were used to identify the underlying transcriptional regulation mechanisms.Two transcription factors,ZbbHLH2 and ZbERF6,were identified as key regulators of monoterpenoid synthesis in Z.bungeanum that upregulate various monoterpenoid synthesis-associated genes and are novel transcriptional activators of ZbIDI,which encodes the rate-limiting enzyme in plant monoterpenoid synthesis.Functional analysis revealed that the expression of three genes[1]modulates monoterpenoid accumulation in Z.bungeanum peel.These findings provide novel insights into the metabolic regulatory network of monoterpenoid synthesis in Z.bungeanum peel,offer potential strategies for the biofortification of specific monoterpenoids,and will promote the development of Z.bungeanum germplasm for targeted breeding and quality improvement. 展开更多
关键词 Zanthoxylum bungeanum Monoterpenoid biosynthesis ZbIDI ZbERF6 ZbbHLH2 transcription regulation MEP pathway
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雷公藤红素干预Transcription Factor EB介导的溶酶体生物发生障碍抑制白内障形成的分子机制
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作者 祁春梅 李秀慧 张智慧 《昆明医科大学学报》 2026年第3期45-53,共9页
目的 探讨雷公藤红素(celastrol,Cel)是否通过激活转录因子EB(transcription factor EB,TFEB)介导的溶酶体生物生成途径,从而抑制白内障的形成。方法 采用H_(2)O_(2)诱导的人晶状体上皮细胞氧化应激模型和亚硒酸盐诱导的大鼠白内障模型... 目的 探讨雷公藤红素(celastrol,Cel)是否通过激活转录因子EB(transcription factor EB,TFEB)介导的溶酶体生物生成途径,从而抑制白内障的形成。方法 采用H_(2)O_(2)诱导的人晶状体上皮细胞氧化应激模型和亚硒酸盐诱导的大鼠白内障模型,将细胞分为对照组、模型组、Cel干预组、Cel+TFEB siRNA组或Cel+MHY1485组(n=5);45只仔鼠分为对照组、模型组、Cel低、中、高剂量组(n=9)。采用CCK-8法检测细胞活力;免疫荧光染色观察TFEB核转位;Western blot检测LAMP1、CTSB蛋白表达;LysoTracker Red染色评估溶酶体数量;裂隙灯显微镜观察并分级(Bahmani标准)晶状体混浊程度;HE染色观察晶状体组织形态。同时利用TFEB siRNA和mTOR激活剂(MHY1485)验证Cel的作用机制。结果 与模型组相比,Cel干预组TFEB核转位效率显著提高了约2.1倍(P<0.000 1),显著上调了溶酶体功能相关蛋白的表达(P<0.001)。LysoTracker Red染色显示,Cel干预使H_(2)O_(2)诱导的溶酶体数量减少得以逆转(P<0.000 1)。在动物模型中,Cel干预显著降低了晶状体混浊程度(P<0.05)。上述Cel的积极作用均可被TFEB siRNA或mTOR激活剂MHY1485显著拮抗(P<0.001)。结论 Cel通过抑制mTOR信号促进TFEB核转位,增强溶酶体生物发生,改善晶状体蛋白稳态,从而抑制白内障形成。 展开更多
关键词 雷公藤红素 转录因子EB 溶酶体 白内障 MTOR
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The regulatory network composed of phytohormones,transcription factors and non-coding RNAs is involved in the flavonoids biosynthesis of fruits
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作者 Xiaoyuan Zheng Xuejiao Zhang Fankui Zeng 《Horticultural Plant Journal》 2026年第3期497-508,共12页
Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the reg... Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established. 展开更多
关键词 Flavonoids biosynthesis PHYTOHORMONE transcription factor Non-coding RNAs Regulation network Fruit
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A novel bHLH transcription factor LlbHLH12 negatively regulates anthocyanin biosynthesis during Lycoris longituba petal development
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作者 Keyi Feng Hongyan Tan +4 位作者 Ling Zhou Tingting Shi Lianggui Wang Yuanzheng Yue Xiulian Yang 《Horticultural Plant Journal》 2026年第3期690-703,共14页
Flower color is an essential trait in ornamental plant breeding. Lycoris longituba is a popular ornamental plant native to central eastern China. The decrease in anthocyanin accumulation causes L. longituba petal colo... Flower color is an essential trait in ornamental plant breeding. Lycoris longituba is a popular ornamental plant native to central eastern China. The decrease in anthocyanin accumulation causes L. longituba petal color fading during flower development, which considerably affects the ornamental value of L. longituba. However, mechanisms underlying anthocyanin biosynthesis inhibition during L. longituba petal development remain unclear. In this study, three LlDFR genes were confirmed to be involved in anthocyanin biosynthesis and LlDFRc exerted the strongest promoting effect on anthocyanin accumulation. According to the correlation analysis results, LlbHLH12 exhibited the strongest negative correlation with LlDFRc. Quantitative real-time PCR analysis showed that LlbHLH12 was highly expressed during the medium bud and full bloom stages of flower development. LlbHLH12 was identified as a member of subgroup XII of bHLH transcription factor family. Subcellular localization and transcriptional activation ability assay revealed that LlbHLH12 was located in the nucleus without transcriptional activation activity. Overexpression of LlbHLH12 in Nicotiana tabacum and L. longituba inhibited anthocyanin accumulation by suppressing the expression of anthocyanin biosynthetic pathway genes. Furthermore, yeast one-hybrid, dual-luciferase, and β-glucuronidase activity assays showed that LlbHLH12 directly bound to the promoters of LlPAL and LlDFRc and suppressed their expression to inhibit anthocyanin biosynthesis. Overall, our study identified a novel bHLH repressor negatively regulating anthocyanin biosynthesis and provided new insights into the molecular mechanisms underlying color fading in L. longituba petals. 展开更多
关键词 Lycoris longituba bHLH transcription factor Negative regulation Anthocyanin biosynthesis Flower color
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ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via Driving DHFR Transcriptional Activation
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作者 Yongle Qiu Kunshan Li +5 位作者 Wenjing Wang Wenjuan Zhang Jilun Liu Yang Bai Fei Xu Jie Guo 《Oncology Research》 2026年第1期458-478,共21页
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism... Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC. 展开更多
关键词 Oral squamous cell carcinoma vasculogenic mimicry METASTASIS dihydrofolate reductase ETS transcription factor ELK4
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Transcription factor CsHSFB2c suppresses CsTS1 and CsGS1 expression to reduce theanine biosynthesis in tea plants under heat stress
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作者 Qihong Zou Bokun Zhou +7 位作者 Yilan Hu Ping Li Qi Zhao Hu Tang Yujie Jiao Xinzhuan Yao Lin Chen Litang Lü 《Journal of Integrative Agriculture》 2026年第3期1009-1019,共11页
Heat stress reduces theanine content in tea plants,but the underlying molecular mechanism remains unclear.In this study,a temperature gradient treatment(20℃,25℃,30℃,and 35℃)was performed to unveil the effect of he... Heat stress reduces theanine content in tea plants,but the underlying molecular mechanism remains unclear.In this study,a temperature gradient treatment(20℃,25℃,30℃,and 35℃)was performed to unveil the effect of heat stress on biosynthesis and accumulation of theanine.We found that heat stress induced metabolic changes,characterized by decreased theanine content and increased catechin levels.In addition,heat stress up-regulated the expression of the class B heat shock transcription factor gene CsHSFB2c,while significantly suppressing the transcription of key theanine biosynthetic genes CsTS1 and CsGS1.Functional studies showed that silencing CsHSFB2c increased theanine content,while its overexpression significantly decreased theanine levels.Consistent with these changes,silencing CsHSFB2c upregulated the expression of CsTS1 and CsGS1,while overexpression of CsHSFB2c downregulated their expression.Yeast one-hybrid(Y1H)and dual-luciferase reporter gene(Dual-LUC)assays showed that CsHSFB2c directly binds to the promoters of CsTS1 and CsGS1 and inhibits their expression.These results demonstrate that CsHSFB2c mediates heat-induced suppression of theanine biosynthesis by directly inhibiting the expression of CsTS1 and CsGS1.This study provides a theoretical basis for improving the heat resistance and quality of tea plants via molecular breeding. 展开更多
关键词 tea plant high temperature heat shock transcription factor(HSF) glutamine synthetase theanine synthetase
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Transcription factor NR2F1 is involved in Parkinson's disease
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作者 Annemarie de Vries Silvia Bolognin 《Neural Regeneration Research》 2026年第7期2930-2931,共2页
Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimeriz... Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023). 展开更多
关键词 transcription factor coup tf NR F nuclear receptor subfamily dimerizes bind dna Parkinsons disease orphan receptor nuclear receptor
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SMAD7 regulates the canonical Wnt signaling through TGF-β cascade crosstalk and SMAD7/β-CATENIN transcription factor complex formation during tooth regeneration
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作者 Qiuyu Chen Zhi Liu +4 位作者 Bohuai Zhou Cheng Liang Yiping Chen Weidong Tian Tian Chen 《International Journal of Oral Science》 2026年第1期103-114,共12页
Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playin... Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering. 展开更多
关键词 Dental stem cells Wnt catenin signaling signaling pathways transcription factors Tooth regeneration tooth morphogenesis maintaining tissue homeostasis TGF cascade
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Vaccinia-related kinase 1/snail family transcriptional repressor 1 regulates epithelial-mesenchymal transition and inflammation in proliferative vitreoretinopathy
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作者 Ying Ying Xin Liao 《International Journal of Ophthalmology(English edition)》 2026年第3期443-454,共12页
AIM:To investigate whether vaccinia-related kinase 1(VRK1)mediates transforming growth factor-beta2(TGF-β2)-caused epithelial-mesenchymal transition(EMT)and inflammatory responses in retinal pigment epithelial(RPE)ce... AIM:To investigate whether vaccinia-related kinase 1(VRK1)mediates transforming growth factor-beta2(TGF-β2)-caused epithelial-mesenchymal transition(EMT)and inflammatory responses in retinal pigment epithelial(RPE)cells through regulating snail family transcriptional repressor 1(SNAI1),and to validate its role in a proliferative vitreoretinopathy(PVR)mouse model.METHODS:Human RPE cell line ARPE-19 cells were treated with TGF-β2 to construct an EMT model.Western blot detected VRK1 level.The effects of VRK1 on SNAI1 expression and biological behavior of ARPE-19 cells were detected by immunofluorescence,ELISA,Transwell,and scratch assay,and the interaction between VRK1 and SNAI1 was confirmed through immunoprecipitation.A PVR mouse model was constructed,and the effects of VRK1 or/and SNAI1 on retinal damage were assessed by pathologic staining.Inflammatory factors and EMT-related proteins were assessed with ELISA and Western blot.RESULTS:VRK1 was upregulated in ARPE-19 cells after TGF-β2 treatment.Overexpression of VRK1 increased cell viability,promoted cell migration and EMT,and the levels of inflammatory factors.Silencing of VRK1 reversed the above indexes.There was a direct interaction between VRK1 and SNAI1,and overexpresssion SNAI1 weakened the impacts of silencing of VRK1.In PVR mice,silencing of VRK1 ameliorated retinal structural damage,decreased proinflammatory factor levels,and suppressed SNAI1 and mesenchymal marker expression.SNAI1 overexpression antagonized the protective effects of silencing VRK1 and exacerbated EMT and inflammatory responses.CONCLUSION:VRK1 plays a key role in retinal structural and inflammatory damage in PVR mice by regulating SNAI1 and mediating TGF-β2-caused EMT and inflammatory responses in RPE cells. 展开更多
关键词 proliferative vitreoretinopathy vacciniarelated kinase 1 epithelial-mesenchymal transition INFLAMMATION snail family transcriptional repressor 1 retinal pigment epithelial cells MICE
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Integrative Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Novel Transcription Factor Regulating Endothelial Heterogeneity Induced by Lrg1 Following Cerebral Ischemia-Reperfusion
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作者 Shaofeng Xiong Wenkai Lv +4 位作者 Guosheng Cao Longsheng Fu Wen Liu Mengfan Lei Yanni Lv 《BIOCELL》 2026年第1期248-272,共25页
Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways ... Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway. 展开更多
关键词 Single-cell RNA sequencing endothelial heterogeneity leucine-rich alpha-2 glycoprotein 1 zinc finger MIZ-type containing 1 Protein Frizzled 3 transcription factor cerebral ischemia reperfusion
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Integrative bulk and single-cell transcriptome analyses reveal RNA modification-related biomarkers of spinal cord injury
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作者 Shixue Huang Kun Jiao +5 位作者 Keqing Li Jiayan Yuan Haoming Shu Yinuo Zhang Xin Zhou Xuhui Zhou 《Neural Regeneration Research》 2026年第7期3249-3266,共18页
Aberrant RNA modification has been linked to the pathogenesis of various diseases;however,its specific molecular mechanisms in spinal cord injury remain poorly understood.The objective of this study was to explore RNA... Aberrant RNA modification has been linked to the pathogenesis of various diseases;however,its specific molecular mechanisms in spinal cord injury remain poorly understood.The objective of this study was to explore RNA modification-related biomarkers of spinal cord injury.The mRNA expression profiles of mice with spinal cord injury were retrieved from the Gene Expression Omnibus(GEO)database(GSE18179).We identified 185 differentially expressed genes using bioinformatics approaches.Functional enrichment analysis demonstrated aberrant activation or inhibition of common metabolism-related pathways,including sulfur metabolism and steroid biosynthesis,in mice with spinal cord injury.An integrated strategy comprising weighted gene co-expression network analysis,a random forest model,a support vector machine model,and a generalized linear model was employed to identify four genes whose aberrant RNA modification was linked to spinal cord injury:Elovl6,Idi1,Sqle,and Stbd1.We verified the expression levels and diagnostic performance of these four genes in the original training dataset and mouse samples via receiver operating characteristic curve analysis.Quantitative reverse transcription-polymerase chain reaction demonstrated variations in the mRNA levels of the four genes between the Sham and spinal cord injury groups at different time points following injury.We also constructed microRNA-mRNA and transcription factor-mRNA interaction networks using Cytoscape.Additionally,we evaluated the proportions of 22 types of immune cells in the spinal cords of mice using the CIBERSORT tool,revealing significant alterations in the numbers of memory B cells,resting dendritic cells,M0 macrophages,activated mast cells,resting mast cells,and CD8+T cells in spinal cord injury mice compared with Sham controls.Microglia and T cells were identified as key cell types by single-cell sequencing analysis.These findings provide new directions for the development of RNA modification-related therapeutic strategies for spinal cord injury and suggest that Elovl6,Idi1,Sqle,and Stbd1 are potential biomarkers of spinal cord injury. 展开更多
关键词 biomarkers machine learning microRNA-mRNA(miRNA-mRNA)network RNA sequencing RNA modification single-cell sequencing analysis spinal cord injury transcription factor-mRNA network weighted gene co-expression network analysis
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BHLHE40 Is a Transcriptional Regulatory Target of NFE2L3 in Triple-Negative Breast Cancer
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作者 Shail Rakesh Modi Terrick Andey George Acquaah-Mensah 《Oncology Research》 2026年第2期346-378,共33页
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
关键词 Nuclear factor erythroid 2-like 3(NFE2L3/NRF3) basic helix-loop-helix family member E 40(BHLHE40/DEC1) triple-negative breast cancer transcriptional regulatory networks master regulators
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Heat shock transcription factors regulate thermotolerance gene networks in tomato(Solanum lycopersicum)flower buds 被引量:2
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作者 Hongwei Li Yun Liu +8 位作者 Yongyao Li Qinqin Yang Tailai Yang Zhi Zhou Yafei Li Na Zhang Yaqing Lyu Yingfang Zhu Tao Lin 《Horticultural Plant Journal》 2025年第1期199-210,共12页
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
关键词 TOMATO Heat stress transcriptOME transcription factor THERMOTOLERANCE
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Integration of transcriptome and metabolome reveals regulatory mechanisms of volatile flavor formation during tomato fruit ripening 被引量:1
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作者 Zhiqiang Liu Jianxin Wu +5 位作者 Licai Wang Xiaonan Lu Golam Jalal Ahammed Xiaolan Zhang Xia Cui Haijing Wang 《Horticultural Plant Journal》 2025年第2期680-692,共13页
Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile fla... Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile flavors of tomatoes is still not clear.Here,we integrated the metabolome and transcriptome of the volatile flavors in tomato fruit to explore the regulatory mechanism of volatile flavor formation,using wild and cultivated tomatoes with significant differences in flavors.A total of 35 volatile flavor compounds were identified,based on the solid phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS).The content of the volatiles,affecting fruit flavor,significantly increased in the transition from breaker to red ripe fruit stage.Moreover,the total content of the volatiles in wild tomatoes was much higher than that in the cultivated tomatoes.The content variations of all volatile flavors were clustered into 10 groups by hierarchical cluster and Pearson coefficient correlation(PCC)analysis.The fruit transcriptome was also patterned into 10 groups,with significant variations both from the mature green to breaker fruit stage and from the breaker to red ripe fruit stage.Combining the metabolome and the transcriptome of the same developmental stage of fruits by co-expression analysis,we found that the expression level of 1182 genes was highly correlated with the content of volatile flavor compounds,thereby constructing two regulatory pathways of important volatile flavors.One pathway is tetrahydrothiazolidine N-hydroxylase(SlTNH1)-dependent,which is regulated by two transcription factors(TFs)from the bHLH and AP2/ERF families,controlling the synthesis of 2-isobutylthiazole in amino acid metabolism.The other is lipoxygenase(Sl LOX)-dependent,which is regulated by one TF from the HD-Zip family,controlling the synthesis of hexanal and(Z)-2-heptenal in fatty acid metabolism.Dual-luciferase assay confirmed the binding of b HLH and AP2/ERF to their structural genes.The findings of this study provide new insights into volatile flavor formation in tomato fruit,which can be useful for tomato flavor improvement. 展开更多
关键词 TOMATO Volatile flavor transcriptOME transcription factor CO-EXPRESSION
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Molecular Cloning,Subcellular Localization and Expression Analyses of PdbHLH57 Transcription Factor in Colored-Leaf Poplar
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作者 Yuhang Li Li Sun +6 位作者 Tao Wang Bingjun Yu Zhihong Gao Xiaochun Shu Tengyue Yan Weibing Zhuang Zhong Wang 《Phyton-International Journal of Experimental Botany》 2025年第4期1211-1223,共13页
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
关键词 transcription factors PdbHLH57 subcellular localization transcription activation analysis expression pattern colored-leaf poplar
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Unraveling the Functional Diversity of MYB Transcription Factors in Plants:A Systematic Review of Recent Advances
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作者 Imene Tatar Caliskan George Dzorgbenya Ametefe +4 位作者 Aziz Caliskan Su-EeLau Yvonne Jing Mei Liew Nur Kusaira Khairul Ikram Boon Chin Tan 《Phyton-International Journal of Experimental Botany》 2025年第8期2229-2254,共26页
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
关键词 Plant growth regulation MYB transcription factors abiotic stress tolerance transcriptional regulation genetic engineering crop improvement
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Comparative transcriptomics analysis reveals stage-specific gene expression profiles associated with gamete formation in Garlic
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作者 Jie Ge Jide Fan +7 位作者 Yongqiang Zhao Xinjuan Lu Canyu Liu Biwei Zhang Qingqing Yang Mengqian Li Yan Yang Feng Yang 《Horticultural Plant Journal》 2025年第2期839-853,共15页
Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory... Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory networks is therefore important for fertility restoration.In this work,we conducted a detailed phenotypic analysis of fertile and sterile garlic genotypes and found that enlargement of topset in the inflorescence of sterile genotypes led to abnormal flowers.Additional cytological observations showed that aberrant meiotic cytokinesis in sterile garlic ultimately resulted in pollen degeneration.Transcriptomics analysis of sterile and fertile genotypes identified possible molecular mechanisms underlying gamete abortion.A total of 100710 differentially expressed genes(DEGs)between the fertile and sterile garlic flowers at three stages of gamete development were identified,many of which were involved in homologous chromosome synapsis during meiosis,MYB transcription factor regulation,ribosome biogenesis and plant hormone signal transduction.Taken together,these results provide insight into the molecular mechanisms and regulatory networks underlying gamete development in garlic and point to a set of candidate genes for further functional characterization. 展开更多
关键词 Allium sativum L. STERILITY MEIOSIS Genome expression transcription factor transcriptOME Ribosome biogenesis
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Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy 被引量:1
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作者 Samuel Abokyi Dennis Yan-yin Tse 《Neural Regeneration Research》 SCIE CAS 2025年第2期366-377,共12页
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
关键词 age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma NEUROMODULATION PHAGOCYTOSIS photoreceptor outer segment degradation retinal aging transcription factor EB
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Puccinia triticina effector Pt-1234 modulates wheat immunity by targeting transcription factor TaNAC069 via its C subdomain 被引量:2
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作者 Huaimin Geng Yanjun Zhang +5 位作者 Zhen Qin Shen Wang Changshan Liu Zhongchi Cui Daqun Liu Haiyan Wang 《The Crop Journal》 2025年第1期69-78,共10页
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
关键词 EFFECTORS NAC transcription factor Host-induced gene silencing Puccinia triticina Triticum aestivum
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