POU4F1

更新于：2025-05-07

基本信息

别名

Brain-3A、Brain-specific homeobox/POU domain protein 3A、Brn-3A

+ [8]

简介

Multifunctional transcription factor with different regions mediating its different effects. Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes. Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor. Activates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins. Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity. May positively regulate POU4F2 and POU4F3. Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Plays a role in TNFSF11-mediated terminal osteoclast differentiation. Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site. Able to act as transcription factor, cannot regulate the expression of the same subset of genes than isoform 1. Does not have antiapoptotic effect on neuronal cells.

关联

100 项与 POU4F1 相关的临床结果

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100 项与 POU4F1 相关的转化医学

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0 项与 POU4F1 相关的专利（医药）

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项与 POU4F1 相关的文献（医药）

2025-04-01·Genes & Genomics

BRN3A, a transcription factor, regulates the expression of genes involved in biological processes shaping the HPV induced cervical cancer

Article

作者: Roy, Jagat Kumar ; Prakash, Anand ; Patel, Yashvant

BACKGROUNDCervical cancer is the fourth most common cancer worldwide in females. This occurs primarily due to the infection of high-risk Human Papilloma Virus (HPV), although in advanced stages it requires support from host cellular factors. BRN3A is one such host cellular factors, whose expression remains high in cervical cancers and upregulates tumorigenic HPV gene expression. The effect of BRN3A on HPV-mediated cervical cancer and the underlying mechanism remains obscure.OBJECTIVETo investigates the effect of BRN3A on cancer-promoting biological processes in HPV-positive uterine cervix cancer cells.METHODSWe have altered the expression of BRN3A through over-expression (OE) and knock-down (KD) constructs in cervical cancer cell line, SiHa, and did transcriptome profiling through next-generation RNA-sequencing, validation through RT-PCR and BRN3A binding study with in silico promoter study and ChIP PCR methods.RESULTSThis study revealed a substantial change in the expression of several genes associated with cancer-promoting biological processes including viral processes, immune response, cell-death, cell-proliferation, different signaling pathways, etc. Additionally, promoter analysis through in silico mode revealed that a total of 32.7% of genes possess BRN3A binding sites at their promoters. Physical interaction of BRN3A with IFITM1, OAS3, ISG15, BCL2L1 and HSP90AB1 genes was also confirmed.CONCLUSIONSThe present study identified molecular targets of BRN3A and provided new insight into the pathogenesis of cervical cancer. According to our knowledge, this is the first report on the effect on eukaryotic transcriptomes after over-expression and knocking down BRN3A.

2025-04-01·Hormone and Metabolic Research

Prognostic Assessment and Analysis of Underlying Biological Mechanisms of Prostate Cancer Based on Estrogen-Related Genes

Article

作者: Xu, Min ; Yang, Qing ; Zhang, Heng ; Fan, Meng-Die ; Hu, Yang ; Jiang, Jia-Wei

AbstractProstate cancer (PCa) ranks among the most prevalent cancers in men, noted for its high mortality rate and unfavorable prognosis. Estrogen-related genes (ERGs) are significantly associated with the progression of PCa. This investigation aims to comprehensively assess the prognosis of PCa based on ERGs and explore its underlying biological mechanisms. Univariate, multivariate, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were conducted to identify prognostic signature genes and build a prognostic model. The model’s predictive performance was assessed using Receiver Operating Characteristic (ROC) curve analysis. Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to investigate the underlying molecular mechanisms of PCa. Antitumor drugs with high sensitivity were predicted using the CellMiner database and the pRRophitic package. Additionally, miRNAs targeting the identified signature genes were predicted using the miRNet database. This study identified six ERGs as prognostic biomarkers for PCa: POU4F1, BMP2, PGF, GAS1, GNAZ, and FGF11. The findings indicated that individuals in the low-risk category exhibited improved prognostic results. Notably, PCa progression may be closely linked to the cell adhesion molecule pathway and epigenetic regulation. Additionally, hsa-let-7a-5p and hsa-miR-34a-5p were identified as potential therapeutic regulators for PCa treatment. In conclusion, this research offers novel perspectives into the progression of PCa, providing robust scientific support for the development of personalized treatment strategies for PCa patients.

2025-04-01·Biomedicine & Pharmacotherapy

The action of 7,8-dihydroxyflavone preserves retinal ganglion cell survival and visual function via the TrkB pathway in NMDA-induced retinal excitotoxicity

Article

作者: Avilés-Trigueros, Marcelino ; Vidal-Sanz, Manuel ; de la Villa, Pedro ; Gallego-Ortega, Alejandro ; Vidal-Villegas, Beatriz ; Galindo-Romero, Caridad ; Bernal-Garro, José Manuel

PURPOSETo analyze the response of different retinal ganglion cell (RGC) populations to NMDA-induced retinal excitotoxicity and the effect of an intraperitoneal treatment with 7,8-Dihydroxyflavone (DHF), a potent selective TrkB agonist.METHODSAdult albino rats were treated the day prior to NMDA injection and the three following days with intraperitoneal vehicle (1 %DMSO in 0.09 %NaCl) or DHF (5 mg/kg in vehicle) injections. DHF-afforded protection was studied in the population of Brn3a⁺RGCs, OPN⁺RGCs (α-RGCs), OPN⁺ Tbr2⁺RGCs (αONs-RGCs), OPN⁺ Tbr2^-Brn3a^-RGCs (αONt-RGCs) and OPN⁺Brn3a⁺RGCs (αOFF-RGCs) at 3,7,14, or 21 days. The functional response was analyzed longitudinally with full-field electroretinograms. The mechanisms underlying DHF-afforded neuroprotection were assessed by western blot (WB) analysis of the levels of phosphorylated and total TrkB, phosphatidylinositol 3 kinase (PIK3/AKT) and mitogen-activated protein kinase (MAPK).RESULTSNMDA intravitreal injection resulted in a significant diminution of the mean amplitudes of the pSTR and b-waves, as well as in severe depletion of all RGCs studied except αONt-RGCs. DHF treatment resulted in rescued mean amplitudes of the pSTR and b-waves up to 21 days after NMDA. WB analysis revealed an increase in p-TrkB which correlates to the increase of TRKB protein and an increase in normalized pAKT/AKT. pMAPK/MAPK was upregulated earlier and significantly higher in DHF-treated retinas. DHF afforded survival of up to 49 % of the Brn3a⁺RGCs versus 25 % of the vehicle group at 21 days after NMDA, and improved survival of the α-RGC and αONs-RGCs but did not rescue the αOFF-RGCs.CONCLUSIONDifferent RGC types exhibit variable susceptibilities to NMDA injury, and DHF-mediated activation of TrkB affords neuroprotection.

项与 POU4F1 相关的新闻（医药）

2024-03-19

·生物探索

Adv Sci | 中山大学聂燕/黄迪/杨林槟/宋尔卫等合作发现基底样乳腺癌的潜在治疗新靶点

引言基底样乳腺癌(BLBC)是乳腺癌中最具侵袭性的分子亚型，预后较差，治疗选择较少。BLBC转录失调及其上游转录因子(TFs)的潜在机制尚不清楚。2024年3月16日，中山大学聂燕、黄迪、杨林槟及宋尔卫等合作在Advanced Science在线发表题为“Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer”的研究论文，在生物信息学分析确定的BLBC高活性候选TFs中，POU4F1在BLBC中唯一上调，并与不良预后相关。POU4F1通过直接结合CDK2和CCND1启动子调节G1/S转变，是BLBC肿瘤生长和恶性表型所必需的。更重要的是，POU4F1通过CDK2介导的EZH2磷酸化和随后的ESR1启动子中的H3K27me3修饰来抑制ERα表达，从而维持BLBC的身份。敲除BLBC细胞中的POU4F1重新激活功能性ERα表达，使BLBC对他莫昔芬治疗敏感。深入的表观遗传学分析表明，POU4F1启动子中二价染色质的亚型特异性重新配置和激活有助于其在BLBC中的独特表达，并由DNA去甲基化酶TET1维持。这些结果揭示了亚型特异性表观遗传激活的TF在促进和维持BLBC中起关键作用，表明POU4F1是BLBC的潜在治疗靶点。乳腺癌是世界上最常见的癌症，在2020年首次超过肺癌。基底样乳腺癌(Basal-like breast cancer, BLBC)，约占乳腺癌的15%-20%，是根据乳腺癌的转录程序进行分类的，具有增殖活性高、细胞周期检查点失调的特点。约75%的BLBC为三阴性乳腺癌(TNBCs)，不表达雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2 (HER2)。因此，内分泌治疗和HER2靶向治疗是无效的，手术和化疗仍然是主要的治疗方法。BLBC本身具有侵袭性的临床行为，再加上缺乏有效的分子靶点，导致BLBC预后不良。尽管有大量关于BLBC的遗传信息，但没有明确的BLBC遗传致癌驱动因素。因此，探索BLBC的发生和发展机制对于发现新的BLBC治疗靶点至关重要。POU4F1在BLBC中表达上调，与预后不良相关（Credit: Advanced Science）转录失调是癌症的一个标志，可能是癌症发生和发展的重要驱动因素。越来越多的研究证实，转录程序失调可由转录因子(transcription factors, TFs)主导，它是参与基因转录调控的关键蛋白。有限的TFs在特定癌症类型中过度活跃，代表了一类独特的药物靶点。例如，ERα是调节乳腺癌腔内表型的主要TFs之一，也是内分泌治疗的关键靶点。然而，BLBC的主要TFs和潜在的调控机制仍不清楚。TFs特异性结合基因组启动子和增强子的DNA序列。越来越多的研究表明，TF结合增强子区域在DNA甲基化谱中发生了显著改变，并与细胞类型特异性基因表达密切相关。在乳腺癌中，增强子区域的异常DNA甲基化已被证明与不同的分子亚型相关。因此，癌症特异性TF可以从含有假定的TF结合位点的增强子区域的DNA甲基化谱中推断出来。该研究旨在研究BLBC特异性TFs在调节肿瘤进展中的作用，以探索针对BLBC的新治疗策略。原文链接https://onlinelibrary.wiley.com/doi/10.1002/advs.202307660责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

抗体药物偶联物临床结果

2024-03-17

·今日头条

乘胜追击！中山大学发文：揭示乳腺癌靶向治疗新策略

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：基底细胞样乳腺癌(BLBC)是乳腺癌中最具侵袭性的分子亚型，预后较差，治疗方案较少。BLBC转录失调的潜在机制及其上游转录因子(TFs)仍不清楚。 3月16日，中山大学研究人员在期刊《Advanced Science》上发表了研究论文，题为“Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer”。本研究结果揭示了亚型特异性表观遗传激活的TF在促进和维持BLBC中起关键作用，表明POU4F1是BLBC的潜在治疗靶点。 https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202307660 研究背景 01 乳腺癌是全球最常见的癌症，2020年首次超越肺癌。基底细胞样乳腺癌(BLBC)占乳腺癌的15%-20%，根据乳腺癌的转录程序进行分类，具有高增殖活性和细胞周期检查点失调的特点。大约75%的BLBC是三阴性乳腺癌(TNBC)，不表达雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)。因此，内分泌治疗和HER2靶向治疗无效，手术和化疗仍然是主要的治疗方法。BLBC的固有侵袭性临床行为，加上缺乏有效的分子靶点，导致BLBC的预后不良。尽管BLBC的遗传信息丰富，但尚未发现BLBC的明确遗传致癌驱动因素。因此，探索BLBC的发生和发展机制对于发现新的治疗靶点至关重要。转录失调是癌症的标志，可作为癌症发生和进展的重要驱动因素。越来越多的研究证实，转录失调程序可以由转录因子(TF)控制，这些转录因子是参与基因转录调控的关键蛋白质。有限的TFs在特定的癌症类型中过度活跃，代表了一种独特的药物靶标。例如，ERα是调节乳腺癌腔内表型的主要TF之一，也是内分泌治疗的关键靶标。然而，BLBC的主要TF及其潜在的调控机制仍不清楚。研究发现 02 为了研究POU4F1在BLBC中的生物学功能，研究人员首先通过qRT-PCR和蛋白质印迹验证了POU4F1在BLBC细胞系中的独特高表达。然后通过两个独立的小干扰RNA(siRNA)在BLBC细胞系中沉默POU4F1，并使用qRT-PCR和蛋白质印迹验证沉默效率。通过CCK8细胞增殖实验和EdU实验确定，沉默POU4F1显著抑制BLBC细胞的生长。此外，沉默POU4F1在实验中均显著降低了BLBC细胞的克隆形成能力，并抑制了BLBC细胞的迁移和侵袭能力，但对BLBC细胞的凋亡没有影响。一致的是，过表达POU4F1增强了BLBC细胞的迁移和侵袭能力。研究人员还将靶向POU4F1的shRNA稳定转导的MDA-MB-231细胞和非靶向对照shRNA分别接种到裸鼠的脂肪垫中。研究结果表明，POU4F1是BLBC肿瘤生长和恶性表型(包括增殖、集落形成、迁移和侵袭)所必需的。 POU4F1是BLBC恶性表型的必要条件数据表明，POU4F1通过激活细胞周期相关通路，主要是G1/S相变，驱动BLBC恶性进展。研究结果还表明,POU4F1通过CDK2/EZH2轴调节ERα表达。另外，靶向POU4F1不仅抑制了BLBC细胞的增殖和转移，而且通过ERα的重新表达和下游信号的再激活，使BLBC异种移植物对内分泌治疗敏感。研究结论 03 总之，研究人员发现POU4F1是BLBC特异性过度活跃的TF，其表达与肿瘤生长和转移相关，导致患者不良预后，靶向POU4F1可抑制BLBC的恶性表型，并重新激活ERα表达，使其具有抗雌激素敏感性，因此，靶向POU4F1可能成为未来结合内分泌治疗BLBC的一种潜在治疗策略。参考资料： https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202307660 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

siRNA临床研究基因疗法临床结果

2023-04-06

·生物谷

研究人员在体外制造出含背/腹侧神经元的脊髓组织

中国科学院遗传与发育生物学研究所戴建武团队在脊髓组织体外制造研究中取得系列进展。该团队建立了含有人神经干细胞和星形胶质细胞的脊髓组织制造技术，在体外实现了厘米级的临床可移植的脊髓组织制造（Jin e 中国科学院遗传与发育生物学研究所戴建武团队在脊髓组织体外制造研究中取得系列进展。该团队建立了含有人神经干细胞和星形胶质细胞的脊髓组织制造技术，在体外实现了厘米级的临床可移植的脊髓组织制造（Jin et al, Bioengineering & Translational Medicine, 2022），并通过材料与细胞共价偶联技术制造了具有药物靶向引导功能的人脊髓组织（Liu et al, Science Advances, 2023）。近期，该团队在脊髓制造研究中取得了新进展。研究通过诱导神经干细胞在胶原材料中预分化，制造出具有背腹侧结构的类脊髓组织（DV-SC），且在移植到大鼠和恒河猴全横断脊髓损伤模型中后显示出良好的治疗效果。研究利用神经分化信号因子组合对接种在胶原支架材料上的神经干细胞进行了为期30天的定向诱导分化，所获得的DV-SC中含有多种类型的脊髓背腹侧神经元，包括BRN3A+ INs（背侧dilc-di3，diLB-di5神经元）、TLX3+ INs（背侧di3，diLB-di5神经元）、LMX1B+ INs（背侧diLB-di5神经元）、LHX1+ INs（腹侧di6-V1神经元）、FOXP2+ INs（腹侧V1神经元）、HB9+及ISL1+（运动神经元）。该研究将DV-SC移植到大鼠和恒河猴T8-9完全性脊髓损伤模型中。DV-SC可以在大鼠和恒河猴损伤区更好地存活，产生成熟的功能性神经元。此外，DV-SC能够对应感觉和运动环路整合到宿主全横断的脊髓神经网络中，其中DV-SC来源的HB9+轴突和BRN3A+轴突可分别和宿主5-羟色胺5-HT+轴突和降钙素基因相关肽CGRP+轴突形成靶向突触连接，部分恢复中断的神经回路，进而改善脊髓损伤大鼠和恒河猴的运动诱发电位和后肢运动功能的恢复。相关研究成果在线发表在Bioactive Materials上。研究工作得到国家自然科学基金重大项目和中科院战略性先导科技专项的支持。

临床研究