Zeb1

Zeb1
  • 文章类型: Journal Article
    促黄体生成素(LH),由垂体促性腺激素细胞产生的异二聚体糖蛋白,调节性腺功能。下丘脑促性腺激素释放激素(GnRH)刺激LH合成和分泌。GnRH通过转录因子诱导LHβ亚基(Lhb)表达,早期生长反应1(EGR1),作用于Lhb启动子。相比之下,锌指E盒结合同源异型盒1(ZEB1)的过表达抑制小鼠LH的产生,但潜在的机制以前没有阐明。这里,我们观察到ZEB1抑制GnRH刺激,但在同源鼠LβT2细胞中没有基础LhbmRNA表达。此外,ZEB1阻断小鼠Lhb的GnRH和/或EGR1诱导,但在这些细胞中没有人LHB启动子-报告基因活性。使用嵌合报告基因,我们绘制了物种特异性ZEB1对序列差异的敏感性,包括Z和E盒,在近端Lhb/LHB启动子中,转录起始位点的上游。在该区域中,ZEB1与鼠Lhb启动子结合的亲和力高于与人LHB启动子结合的亲和力。为了检查ZEB1在LH合成中的生理作用,我们表征了促性腺激素特异性Zeb1基因敲除小鼠。促性腺激素中ZEB1的丢失不影响LH的产生或分泌。总的来说,数据表明ZEB1在过表达时,可以抑制GnRH/EGR1诱导的小鼠Lhb转录,但在小鼠LH合成中没有必要的作用。
    Luteinizing hormone (LH), a heterodimeric glycoprotein produced by pituitary gonadotrope cells, regulates gonadal function. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates LH synthesis and secretion. GnRH induces LHβ subunit (Lhb) expression via the transcription factor, early growth response 1 (EGR1), acting on the Lhb promoter. In contrast, over-expression of zinc finger E-box binding homeobox 1 (ZEB1) represses LH production in mice, but the underlying mechanism was not previously elucidated. Here, we observed that ZEB1 inhibited GnRH-stimulated, but not basal Lhb mRNA expression in homologous murine LβT2 cells. Moreover, ZEB1 blocked GnRH and/or EGR1 induction of murine Lhb, but not human LHB promoter-reporter activity in these cells. Using chimeric reporters, we mapped the species-specific ZEB1 sensitivity to sequence differences, including in Z- and E-boxes, in the proximal Lhb/LHB promoters, immediately upstream of the transcription start sites. ZEB1 bound to the murine Lhb promoter with higher affinity than to the human LHB promoter in this region. To examine ZEB1\'s physiological role in LH synthesis, we characterized gonadotrope-specific Zeb1 knockout mice. Loss of ZEB1 in gonadotropes did not affect LH production or secretion. Collectively, the data suggest that ZEB1, when over-expressed, can inhibit GnRH/EGR1 induction of murine Lhb transcription but does not play a necessary role in LH synthesis in mice.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    结直肠癌(CRC)是全球最常见的恶性肿瘤之一。转移是CRC患者死亡的主要原因。转录因子在转移过程中起关键作用。使用生物信息学工具,我们分析了TCGA-COAD和GES146587数据集,确定ZNF248参与肿瘤进展.通过分析100例CRC患者组织,发现ZNF248在癌组织以及通过qRT-PCR鉴定的CRC细胞系中高表达。我们的研究发现ZNF248增强CRC细胞的迁移和侵袭能力。ZNF248与上皮间质转化(EMT)相关标记(ZEB1,snail1)呈正相关,E-cadherin与ZNF248呈负相关。此外,TCGA数据集的分析表明ZNF248的mRNA水平与ZEB1表达之间存在很强的相关性.此外,发现ZEB1的过表达可以逆转CRC细胞的侵袭和迁移,以及ZNF248RNA干扰诱导的EMT标记表达的抑制。免疫组织化学分析表明ZNF248表达与淋巴结转移有实质性关联。和肝转移(P=0.01,P=0.01),ZNF248和ZEB1表达呈正相关(P=0.021)。使用芯片PCR检测,发现ZNF248与ZEB1启动子区域结合。这些发现表明ZNF248在体内促进CRC转移,通过靶向ZEB1和激活EMT途径揭示了其作为癌基因在CRC中的作用,通过靶向ZEB1为CRC治疗提供了新的和有前途的生物标志物。
    Colorectal cancer (CRC) is one of the most common malignant tumors globally, with metastasis emerging as the leading cause of mortality in CRC patients. Transcription factors play pivotal roles in the metastatic process. Using bioinformatics tools, we analyzed the TCGA-COAD and GES146587 datasets and identified ZNF248 participating in tumor progression. By analyzing 100 CRC patient tissues, it is found that ZNF248 is highly expressed in cancer tissue as well as in CRC cell lines identified by qRT-PCR. Our study discovered that ZNF248 enhances CRC cell migratory and invasive capabilities. A positive correlation was found between ZNF248 and epithelial-mesenchymal transition (EMT)-related markers (ZEB1, snail1), while E-cadherin exhibited a negative correlation with ZNF248. In addition, the analysis of the TCGA dataset demonstrated a strong correlation between the mRNA level of ZNF248 and ZEB1 expressions. Furthermore, it is found that the overexpression of ZEB1 could reverse CRC cell invasion and migration, along with the inhibition on EMT marker expressions induced by the RNA interference with ZNF248. Immunohistochemical analysis indicated a substantial association of ZNF248 expression with the lymph node metastasis, and with the liver metastasis (P =0.01, P =0.01), and a positive correlation between ZNF248 and ZEB1 expression (P =0.021) was also identified. Using Chip-PCR assay, it is found that ZNF248 bound to the ZEB1 promoter region. These findings showed that ZNF248 promotes CRC metastasis in vivo, revealed its role as an oncogene in CRC by targeting ZEB1 and activating the EMT pathway, which provided novel and promising biomarkers for CRC therapy through targeting ZEB1.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    结直肠癌(CRC)是一种侵袭性原发性肠道恶性肿瘤,在全球所有癌症类型中发病率第三高,死亡率第二高。转录因子(TF)由于其识别基因上游的特定DNA序列的能力而调节细胞发育和分化。大量研究表明,TFs之间存在很强的相关性,肿瘤的病因,和治疗方法。这里,我们旨在探索与预后相关的TFs并理解其致癌机制,从而为CRC的诊断和管理提供了新的见解。
    利用癌症基因组图谱数据库鉴定CRC和正常组织之间差异表达的TFs,进行加权相关网络分析和Cox回归分析以鉴定与预后相关的TFs。使用5-乙炔基-2'-脱氧尿苷和CRC细胞中的细胞侵袭测定法确定了hubTF锌指E盒结合同源盒1(ZEB1)的细胞功能。RNA测序,京都基因和基因组富集百科全书,和基因集富集分析用于鉴定ZEB1参与的细胞过程。免疫亲和纯化,银染质谱,并进行染色质免疫沉淀测定以搜索可能与ZEB1和它们共同调节的靶基因相互作用的蛋白质。
    通过生物信息学分析技术鉴定了13种与预后相关的中心TFs。在这些TFs中,ZEB1成为与CRC最密切相关的TF,通过监管网络图的组合确定,存活曲线,和表型分析。ZEB1通过招募NuRD(MTA1)复合物促进CRC细胞生长,和ZEB1/NuRD(MTA1)复合物转录抑制糖酵解相关的肿瘤抑制基因。
    我们的研究不仅确定了与CRC预后相关的中心生物标志物,而且揭示了ZEB1影响癌症进展的特定分子机制。这些见解为CRC的诊断和潜在的治疗机会提供了重要的证据。
    UNASSIGNED: Colorectal cancer (CRC) is an aggressive primary intestinal malignancy with the third-highest incidence and second-highest mortality among all cancer types worldwide. Transcription factors (TFs) regulate cell development and differentiation owing to their ability to recognize specific DNA sequences upstream of genes. Numerous studies have demonstrated a strong correlation between TFs, the etiology of tumors, and therapeutic approaches. Here, we aimed to explore prognosis-related TFs and comprehend their carcinogenic mechanisms, thereby offering novel insights into the diagnosis and management of CRC.
    UNASSIGNED: Differentially expressed TFs between CRC and normal tissues were identified leveraging The Cancer Genome Atlas database, Weighted correlation network analysis and Cox regression analysis were performed to identify prognosis-related TFs. The cellular functions of hub TF zinc finger E-box binding homeobox 1 (ZEB1) were determined using by 5-ethynyl-2\'-deoxyuridine and cell invasion assays in CRC cells. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses were used to identify the cellular processes in which ZEB1 participates. Immunoaffinity purification, silver staining mass spectrometry, and a chromatin immunoprecipitation assay were conducted to search for proteins that might interact with ZEB1 and the target genes they jointly regulate.
    UNASSIGNED: Thirteen central TFs related to prognosis were identified through bioinformatics analysis techniques. Among these TFs, ZEB1 emerged as the TF most closely associated with CRC, as determined through a combination of regulatory network diagrams, survival curves, and phenotype analyses. ZEB1 promotes CRC cell growth by recruiting the NuRD(MTA1) complex, and the ZEB1/NuRD(MTA1) complex transcriptionally represses glycolysis-associated tumor suppressor genes.
    UNASSIGNED: Our study not only identified a hub biomarker related to CRC prognosis but also revealed the specific molecular mechanisms through which ZEB1 affects cancer progression. These insights provide crucial evidence for the diagnosis of CRC and potential treatment opportunities.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    二甲双胍是一种重要的抗糖尿病药物,具有减轻骨骼肌萎缩和促进肌细胞分化的潜力。然而,这些功能的确切分子机制尚不清楚.以前的研究表明,转录因子锌指结合E盒同源盒1(ZEB1),参与肿瘤进展,抑制肌肉萎缩.因此,我们假设二甲双胍的保护作用可能与ZEB1有关。我们在体外和体内通过调节ZEB1研究了二甲双胍对IL-1β诱导的骨骼肌萎缩的积极作用。与正常细胞分化组比拟,二甲双胍治疗组的肌管直径增加,萎缩标记蛋白表达水平降低.此外,肌肉细胞分化受阻,当我们通过ZEB1特异性小干扰RNA(si-ZEB1)人工干扰小鼠骨骼肌成肌细胞(C2C12)中的ZEB1表达时。作为对炎症刺激的反应,二甲双胍治疗增加ZEB1和三种分化蛋白的表达水平,MHC,MyoD,和肌生成素,而si-ZEB1部分抵消了这些影响。此外,在小鼠模型中,通过向下肢的骨骼肌施用脂多糖(LPS)来诱导明显的萎缩。经过4周的胃内给药,二甲双胍治疗可改善肌肉萎缩并增加ZEB1的表达水平。二甲双胍治疗部分缓解肌肉萎缩和刺激分化。总的来说,我们的发现可以更好地了解二甲双胍治疗骨骼肌萎缩的潜在作用机制,并提示二甲双胍作为治疗药物的潜力.
    Metformin is an important antidiabetic drug that has the potential to reduce skeletal muscle atrophy and promote the differentiation of muscle cells. However, the exact molecular mechanism underlying these functions remains unclear. Previous studies revealed that the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), which participates in tumor progression, inhibits muscle atrophy. Therefore, we hypothesized that the protective effect of metformin might be related to ZEB1. We investigated the positive effect of metformin on IL-1β-induced skeletal muscle atrophy by regulating ZEB1 in vitro and in vivo. Compared with the normal cell differentiation group, the metformin-treated group presented increased myotube diameters and reduced expression levels of atrophy-marker proteins. Moreover, muscle cell differentiation was hindered, when we artificially interfered with ZEB1 expression in mouse skeletal myoblast (C2C12) cells via ZEB1-specific small interfering RNA (si-ZEB1). In response to inflammatory stimulation, metformin treatment increased the expression levels of ZEB1 and three differentiation proteins, MHC, MyoD, and myogenin, whereas si-ZEB1 partially counteracted these effects. Moreover, marked atrophy was induced in a mouse model via the administration of lipopolysaccharide (LPS) to the skeletal muscles of the lower limbs. Over a 4-week period of intragastric administration, metformin treatment ameliorated muscle atrophy and increased the expression levels of ZEB1. Metformin treatment partially alleviated muscle atrophy and stimulated differentiation. Overall, our findings may provide a better understanding of the mechanism underlying the effects of metformin treatment on skeletal muscle atrophy and suggest the potential of metformin as a therapeutic drug.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:上皮剪接调节蛋白1(ESRP1)通过与锌指E盒结合蛋白1(ZEB1)和CD44相互作用,通过上皮-间质转化调控肿瘤进展和转移。然而,ESRP1在肝内胆管癌(iCCA)中的作用尚不清楚.
    方法:使用小干扰RNA分析了三种iCCA细胞系(HuCCT-1,SSP-25和KKU-100),以研究ESRP1和ZEB1的分子生物学功能。免疫组化分析iCCA组织中ESRP1和ZEB1的表达与临床病理特征之间的关系。进行蛋白质组分析以鉴定与ESRP1表达相关的分子。
    结果:ESRP1在HuCCT-1和SSP-25细胞中表达上调。细胞迁移和侵袭增强,在ESRP1沉默细胞中,ZEB1和CD44s(CD44标准)亚型的表达上调。此外,ESRP1沉默增加N-cadherin和波形蛋白的表达,表明存在间充质特性。相反,ZEB1沉默增加了ESRP1和CD44v(CD44变体)同种型的表达。免疫组织化学分析显示,较低的ESRP1与ZEB1表达比率与iCCA患者的无复发生存率有关。Flotillin2,一种与上皮-间质转化相关的脂筏标记,在蛋白质组学分析中被鉴定为与交互式反馈环相关的蛋白质。
    结论:ESRP1通过与ZEB1和CD44相互作用以调节上皮-间质转化来抑制iCCA中的肿瘤进展。
    OBJECTIVE: Epithelial splicing regulatory protein 1 (ESRP1) regulates tumor progression and metastasis through the epithelial‒mesenchymal transition by interacting with zinc finger E-box binding 1 (ZEB1) and CD44 in cancers. However, the role of ESRP1 in intrahepatic cholangiocarcinoma (iCCA) remains unclear.
    METHODS: Three iCCA cell lines (HuCCT-1, SSP-25, and KKU-100) were analyzed using small interfering RNA to investigate the molecular biological functions of ESRP1 and ZEB1. The association between clinicopathological features and the expression of ESRP1 and ZEB1 in iCCA tissues was analyzed immunohistochemically. Proteomic analysis was performed to identify molecules related to ESRP1 expression.
    RESULTS: ESRP1 expression was upregulated in HuCCT-1 and SSP-25 cells. Cell migration and invasion were enhanced, and the expression of ZEB1 and CD44s (CD44 standard) isoforms were upregulated in the ESRP1 silencing cells. Moreover, ESRP1 silencing increased the expression of N-cadherin and vimentin, indicating the presence of mesenchymal properties. Conversely, ZEB1 silencing increased the expression of ESRP1 and CD44v (CD44 variant) isoforms. Immunohistochemical analysis revealed that a lower ESRP1-to-ZEB1 expression ratio was associated with poor recurrence-free survival in patients with iCCA. Flotillin 2, a lipid raft marker related to epithelial‒mesenchymal transition, was identified as a protein related to the interactive feedback loop in proteomic analysis.
    CONCLUSIONS: ESRP1 suppresses tumor progression in iCCA by interacting with ZEB1 and CD44 to regulate epithelial‒mesenchymal transition.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    整合子复合物通过RNA聚合酶II(RNAP2)在启动子近端暂停位点的过早终止来减弱基因表达。这是刺激反应所必需的,细胞分化,和神经发育,但整合因子是如何实现基因特异性和适应性调控的,目前尚不清楚.这里,我们确定了人类整合子亚基13/14上的两个位点,它们充当序列特异性转录因子(TF)和其他转录效应复合物的结合中心。当Integrator连接到暂停的RNAP2时,这些集线器位于转录气泡的上游,与TF启动子同时连接一致。TFs与Integrator全基因组共定位,增加目标基因上的整合子丰度,并共同调节反应性转录程序。例如,葡萄糖饥饿诱导的感觉纤毛形成取决于整合因子-TF接触。我们的数据表明,TF介导的整合子启动子募集是靶向转录调控的广泛机制。
    The Integrator complex attenuates gene expression via the premature termination of RNA polymerase II (RNAP2) at promoter-proximal pausing sites. It is required for stimulus response, cell differentiation, and neurodevelopment, but how gene-specific and adaptive regulation by Integrator is achieved remains unclear. Here, we identify two sites on human Integrator subunits 13/14 that serve as binding hubs for sequence-specific transcription factors (TFs) and other transcription effector complexes. When Integrator is attached to paused RNAP2, these hubs are positioned upstream of the transcription bubble, consistent with simultaneous TF-promoter tethering. The TFs co-localize with Integrator genome-wide, increase Integrator abundance on target genes, and co-regulate responsive transcriptional programs. For instance, sensory cilia formation induced by glucose starvation depends on Integrator-TF contacts. Our data suggest TF-mediated promoter recruitment of Integrator as a widespread mechanism for targeted transcription regulation.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    角膜,由三个细胞层和两个非细胞层组成,是眼球的最外面的部分,经常受到外部身体的伤害,化学,和微生物的侮辱。上皮间质转化(EMT)在角膜损伤的修复中起着至关重要的作用。锌指E盒结合homeobox1(ZEB1),参与EMT的重要转录因子,在角膜组织中表达。它调节细胞活动,如迁移,改造,和扩散,从而影响组织炎症,纤维化,肿瘤转移,和坏死通过介导各种主要信号通路,包括转化生长因子(TGF)-β。ZEB1的功能障碍会损害角膜组织修复,导致上皮愈合延迟,间质纤维化,新生血管形成,鳞状细胞化生.了解ZEB1调节角膜损伤修复的潜在机制将有助于我们制定增强角膜损伤修复的治疗方法。
    The cornea, consisting of three cellular and two non-cellular layers, is the outermost part of the eyeball and frequently injured by external physical, chemical, and microbial insults. The epithelial-to-mesenchymal transition (EMT) plays a crucial role in the repair of corneal injuries. Zinc finger E-box binding homeobox 1 (ZEB1), an important transcription factor involved in EMT, is expressed in the corneal tissues. It regulates cell activities like migration, transformation, and proliferation, and thereby affects tissue inflammation, fibrosis, tumor metastasis, and necrosis by mediating various major signaling pathways, including transforming growth factor (TGF)-β. Dysfunction of ZEB1 would impair corneal tissue repair leading to epithelial healing delay, interstitial fibrosis, neovascularization, and squamous cell metaplasia. Understanding the mechanism underlying ZEB1 regulation of corneal injury repair will help us to formulate a therapeutic approach to enhance corneal injury repair.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:PD-L1过表达通常在各种恶性肿瘤中观察到,并且与癌症患者的不良预后密切相关。此外,PD-L1已被证明在促进不同癌症类型的血管生成和上皮间质转化(EMT)过程中起重要作用。
    方法:通过生物信息学方法和免疫组织化学方法探讨PD-L1与血管生成拟态和上皮间质转化(EMT)的关系。通过蛋白质印迹和q-PCR测定评估PD-L1在调节ZEB1表达和EMT过程中的功能。通过伤口愈合评估PD-L1对A549和H1299细胞迁移和增殖能力的影响,细胞入侵,和siRNA介导的PD-L1敲低后的CCK8测定。利用管形成测定来评估VM结构的存在。
    结果:在这项研究中,与正常肺上皮细胞相比,在A549和H1299细胞中观察到PD-L1表达增加。免疫组织化学分析显示,与PD-L1阴性组相比,PD-L1阳性组中VM结构的患病率更高。此外,研究还发现,PD-L1高表达与晚期TNM分期和转移增加显著相关.PD-L1敲除后,NSCLC细胞显示其形成管状结构的能力显著降低。此外,关键EMT和VM相关标记的水平,包括N-钙黏着蛋白,MMP9,VE-钙黏着蛋白,和VEGFA,显著下降,而E-cadherin表达上调。此外,PD-L1或ZEB1敲除后,两种细胞系的迁移和增殖能力均受到显著抑制.
    结论:敲低PD-L1可以抑制ZEB1介导的EMT,从而阻碍了NSCLC中VM的形成。
    BACKGROUND: PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types.
    METHODS: The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures.
    RESULTS: In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown.
    CONCLUSIONS: Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:尽管microRNA(miR)-150-5p参与肾纤维化的进展,其作用机制仍然难以捉摸。
    方法:采用单侧输尿管梗阻小鼠模型。用转化生长因子β1(TGF-β1)刺激人肾2(HK-2)细胞建立体外肾纤维化模型。miR-150-5p的表达谱,锌指E盒绑定homeobox1(ZEB1),以及其他纤维化和上皮间质转化(EMT)连接的蛋白使用Westernblot和定量逆转录聚合酶链反应进行测定。HK-2细胞中miR-150-5p和ZEB1之间的关系通过双荧光素酶报告基因测定来证实。
    结果:体内和体外肾纤维化模型均显示miR-150-5p表达降低和ZEB1水平升高。E-cadherin水平显着下降,以及α平滑肌肌动蛋白(α-SMA)和I型胶原蛋白(Col-I)水平的增加,在TGF-β1处理的HK-2细胞中观察到。miR-150-5p的过表达改善了TGF-β1介导的纤维化和EMT。值得注意的是,miR-150-5p通过直接靶向ZEB1起作用。在ZEB1过表达后,观察到miR-150-5p对TGF-β1介导的HK-2细胞纤维化和EMT的抑制作用的显着逆转。
    结论:MiR-150-5p通过在HK-2细胞中靶向ZEB1抑制TGF-β1诱导的纤维化和EMT,为肾纤维化的治疗干预提供有益的见解。
    BACKGROUND: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive.
    METHODS: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-β1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay.
    RESULTS: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-β1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-β1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-β1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression.
    CONCLUSIONS: MiR-150-5p suppresses TGF-β1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:三阴性乳腺癌(TNBC)是一种异质性和侵袭性疾病,其特征是死亡率高和预后差。据报道,层粘连蛋白γ2(LAMC2)在多种肿瘤中高表达,高表达与癌症的发生发展有关。然而,LAMC2影响TNBC的功能和机制尚不清楚.
    方法:Kaplan-Meier生存分析和免疫组织化学(IHC)染色检测LAMC2在TNBC中的表达水平。随后,细胞活力测定,进行伤口愈合和transwell试验以检测LAMC2在细胞增殖和迁移中的功能。使用异种移植小鼠模型来评估体内LAMC2的致瘤功能。进行荧光素酶报告基因测定和蛋白质印迹以阐明潜在的机制。
    结果:在这项研究中,我们发现,在TNBC队列中,LAMC2的高表达与低生存率显著相关.功能表征显示LAMC2通过上调CD44促进TNBC细胞系的细胞增殖和迁移能力。此外,LAMC2通过调节上皮-间质转化(EMT)标志物的表达在TNBC中发挥致癌作用。荧光素酶报告基因测定证实LAMC2靶向ZEB1以促进其转录。有趣的是,LAMC2通过STAT3信号通路调节TNBC细胞迁移。
    结论:LAMC2通过激活CD44/STAT3信号通路靶向ZEB1促进TNBC增殖和迁移,提示LAMC2可能是TNBC患者的潜在治疗靶点。
    BACKGROUND: Triple negative breast cancer (TNBC) is a heterogeneous and aggressive disease characterized by a high risk of mortality and poor prognosis. It has been reported that Laminin γ2 (LAMC2) is highly expressed in a variety of tumors, and its high expression is correlated with cancer development and progression. However, the function and mechanism by which LAMC2 influences TNBC remain unclear.
    METHODS: Kaplan-Meier survival analysis and Immunohistochemical (IHC) staining were used to examine the expression level of LAMC2 in TNBC. Subsequently, cell viability assay, wound healing and transwell assay were performed to detect the function of LAMC2 in cell proliferation and migration. A xenograft mouse model was used to assess tumorigenic function of LAMC2 in vivo. Luciferase reporter assay and western blot were performed to unravel the underlying mechanism.
    RESULTS: In this study, we found that higher expression of LAMC2 significantly correlated with poor survival in the TNBC cohort. Functional characterization showed that LAMC2 promoted cell proliferation and migration capacity of TNBC cell lines via up-regulating CD44. Moreover, LAMC2 exerted oncogenic roles in TNBC through modulating the expression of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay verified that LAMC2 targeted ZEB1 to promote its transcription. Interestingly, LAMC2 regulated cell migration in TNBC via STAT3 signaling pathway.
    CONCLUSIONS: LAMC2 targeted ZEB1 via activating CD44/STAT3 signaling pathway to promote TNBC proliferation and migration, suggesting that LAMC2 could be a potential therapeutic target in TNBC patients.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号