TEAD1/4 exerts oncogenic role and is negatively regulated by miR-4269 in gastric tumorigenesis.
TEAD1/4 exerts oncogenic role and is negatively regulated by miR-4269 in gastric tumorigenesis.
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作者：
Zhou Y;Huang T;Zhang J;Wong CC;Zhang B;Dong Y;Wu F;Tong JHM;Wu WKK;Cheng ASL;Yu J;Kang W;To KF
TEA结构域(TeAD)转录因子是Hippo-YAP1信号通路的关键组成部分，但其功能作用和调控机制尚不清楚。本研究旨在全面探讨TEAD家族在胃癌发生中的表达模式和功能作用，并研究其在microRNAs(MiRNAs)中的调控作用。用定量逆转录-聚合酶链式反应(qRT-PCR)和免疫印迹法检测TEAD家族的mRNA和蛋白表达。它们的功能作用通过体外和体内研究来确定。应用组织芯片免疫组织化学方法研究TEAD4在胃癌中的表达及其临床病理意义。对潜在靶向TEAD1/4的miRNAs的预测是由TargetScan和miRDB进行的。QRT-PCR、Western印迹和荧光素酶检测证实了miRNAs对TEAD1/4的调控。TEAD1/4在胃癌细胞系和原代胃癌组织中高表达。TEAD1/4基因的敲除在体内外均有明显的抗癌作用。TEAD1被证实是miR-377-3p和miR-4269的直接靶标，而TEAD4则受到miR-1343-3p和miR-4269的负调控。其中，miR-4269是TEAD1/4最有效的抑制剂。这些miRNAs的异位表达证实了它们的抑瘤作用。在原发的GC肿瘤中，miR-4269的下调与疾病特异性生存不良相关，并且与TEAD4呈负相关。TEAD1和TEAD4是致癌因子，其异常激活在一定程度上是由miR-377-3p、miR-1343-3p和miR-4269的沉默介导的。首次提出核积聚的TEAD4和下调的miR-4269可作为胃癌预后的新生物标志物。
TEA domain (TEAD) transcription factors are key components of the Hippo–YAP1 signaling pathway, but their functional role and regulatory mechanisms remain unclear. This study aims to comprehensively explore the expression pattern and functional role of TEAD family in gastric carcinogenesis and investigate its regulation by microRNAs (miRNAs). The mRNA and protein expression of TEAD family were examined by quantitative reverse transcription–PCR (qRT–PCR) and western blot. Their functional roles were determined by in vitro and in vivo studies. The clinicopathological association of TEAD4 in gastric cancer (GC) was studied using immunohistochemistry on tissue microarray. The prediction of miRNAs, which potentially target TEAD1/4, was performed by TargetScan and miRDB. The regulation of TEAD1/4 by miRNAs was confirmed by qRT–PCR, western blot and luciferase assays. TEAD1/4 were overexpressed in GC cell lines and primary GC tissues. Knockdown of TEAD1/4 induced a significant anticancer effect in vitro and in vivo. TEAD1 was confirmed to be a direct target of miR-377-3p and miR-4269, while TEAD4 was negatively regulated by miR-1343-3p and miR-4269. Among them, miR-4269 was the most effective inhibitor of TEAD1/4. Ectopic expression of these miRNAs substantiated their tumor-suppressive effects. In primary GC tumors, downregulation of miR-4269 was associated with poor disease-specific survival and showed a negative correlation with TEAD4. TEAD1 and TEAD4 are oncogenic factors, whose aberrant activation are, in part, mediated by the silence of miR-377-3p, miR-1343-3p and miR-4269. For the first time, the nuclear accumulated TEAD4 and downregulated miR-4269 are proposed to serve as novel prognostic biomarkers in GC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.7
作者：
Lim, Byungho;Park, Jong-Lyul;Kim, Seon-Young
通讯作者：
Kim, Seon-Young
模拟 VGLL4 功能的肽作为 YAP 拮抗剂治疗胃癌
影响因子：
50.3
作者：
Jiao, Shi;Wang, Huizhen;Zhou, Zhaocai
通讯作者：
Zhou, Zhaocai
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
SIRT1 调节 YAP2 介导的肝细胞癌细胞增殖和化疗耐药。
影响因子：
8
作者：
Mao, B.;Hu, F.;Bi, W.
通讯作者：
Bi, W.