A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ.
A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ.
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<span><span>microRNA-129-5p 通过直接抑制转录共激活因子 YAP 和 TAZ 抑制卵巢癌细胞增殖和存活的新作用</span></span>
DOI：
10.18632/oncotarget.3254
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发表时间：
2015-04-20
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Tan G;Cao X;Dai Q;Zhang B;Huang J;Xiong S;Zhang Yy;Chen W;Yang J;Li H
转录辅激活因子Yes相关蛋白（雅普）和转录辅激活因子PDZ结合基序（TAZ）是哺乳动物细胞中的关键癌基因。雅普和TAZ的活性在很大程度上通过磷酸化-泛素化机制受到Hippo肿瘤抑制途径的限制。最近报道了microRNA参与癌症进展，尽管它们是否在人类癌细胞中激活雅普和TAZ中起作用仍不清楚。在此，我们报道了一种microRNA，miR-129- 5 p，直接抑制雅普和TAZ的表达，导致TEA结构域（TEAD）转录失活，并下调Hippo下游基因，结缔组织生长因子（CTGF）和细胞周期蛋白A。此外，我们揭示了miR-129- 5 p抑制卵巢癌细胞增殖、存活和致瘤性，并且卵巢癌细胞中miR-129- 5 p的下调与恶性进展和不良存活高度相关。因此，我们证明了癌症中雅普和TAZ激活的新机制，不仅表明miR-129- 5 p在卵巢癌进展中的潜在关键作用，而且还提供了新的治疗策略来规避疾病。
Transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key oncogenes in mammalian cells. Activities of YAP and TAZ are largely restricted by the Hippo tumor suppressor pathway through phosphorylation-ubiquitination mechanisms. The involvement of microRNA in cancer progression has recently been reported, though whether they have a role in activating YAP and TAZ in human cancer cells remains unclear. Here, we report a microRNA, miR-129-5p, directly represses YAP and TAZ expression, leading to the inactivation of TEA domain (TEAD) transcription, and the downregulation of Hippo downstream genes, connective tissue growth factor (CTGF) and Cyclin A. Furthermore, we reveal miR-129-5p inhibits ovarian cancer cell proliferation, survival and tumorigenicity, and that downregulation of miR-129-5p in ovarian cancer cells highly correlates with malignant progression and poor survival. Hence, we demonstrate a novel mechanism for YAP and TAZ activation in cancers, indicating not only a potentially pivotal role for miR-129-5p in the progression of ovarian cancer, but also offering new therapeutic strategies to circumvent the disease.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
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作者：
Jeong, Geun Ok;Shin, Sang Hun;Kim, Jae Ho
通讯作者：
Kim, Jae Ho
EGFR-MAPK信号通过Ajuba家族蛋白来调节河马信号传导。
影响因子：
11.8
作者：
Reddy, B. V. V. G.;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
82.9
作者：
通讯作者：
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DOI：
10.1038/nrd4161
发表时间：
2014-01
期刊：
Nature reviews. Drug discovery
影响因子：
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作者：
通讯作者：
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