miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB.
miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB.
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miR-665 通过靶向 PTPRB 减少 Hippo 信号传导，从而促进肝细胞癌细胞迁移、侵袭和增殖。
DOI：
10.1038/s41419-018-0978-y
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发表时间：
2018-09-20
影响因子：
9
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Hu Y;Yang C;Yang S;Cheng F;Rao J;Wang X
越来越多的证据表明，微小RNA(MiRNA)的异常表达与肝细胞癌的发生发展密切相关。然而，miR-665在肝癌进展中的潜在作用和机制仍然很大程度上是未知的。我们目前的研究表明miR-665在肝癌细胞和组织中表达上调。MiR-665高表达提示肝细胞癌患者肿瘤大小、血管侵犯及Edmondson分级越严重。功能获得或丧失分析表明，miR-665在体内外促进了肝癌细胞的增殖、迁移、侵袭和上皮-间充质转化(EMT)。B型酪氨酸磷酸酶受体(PTPRB)在肝癌组织中表达下调，且与miR-665表达呈负相关。通过Western blotting和荧光素酶报告实验，PTPRB被确定为miR-665的直接下游靶点。PTPRB的修复逆转了miR-665对肝癌迁移、侵袭和细胞增殖的影响。一项机制研究表明，PTRB通过调节Hippo信号通路介导miR-665的功能作用。综上所述，我们的结果提示miR-665是PTPRB的负调控因子，可能通过降低Hippo信号通路的活性来促进肿瘤的增殖和转移，这可能是治疗肝癌的一个潜在靶点。
Growing evidence suggests that aberrant microRNA (miRNA) expression contributes to hepatocellular carcinoma (HCC) development and progression. However, the potential role and mechanism of miR-665 in the progression of liver cancer remains largely unknown. Our current study showed that miR-665 expression was upregulated in HCC cells and tissues. High expression of miR-665 exhibited more severe tumor size, vascular invasion and Edmondson grading in HCC patients. Gain- or loss-of-function assays demonstrated that miR-665 promoted cell proliferation, migration, invasion, and the epithelial–mesenchymal transition (EMT) of HCC cells in vitro and in vivo. Tyrosine phosphatase receptor type B (PTPRB) was downregulated in HCC tissues, and was negatively correlated with miR-665 expression. Through western blotting and luciferase reporter assay, PTPRB was identified as a direct downstream target of miR-665. Restoration of PTPRB reverses the effects of miR-665 on HCC migration, invasion, and cell proliferation. A mechanistic study showed that PTPTRB mediated the functional role of miR-665 through regulation of the Hippo signaling pathway. In conclusion, our results suggested that miR-665 was a negative regulator of the PTPRB and could promote tumor proliferation and metastasis in HCC through decreasing Hippo signaling pathway activity, which can be a potential target for HCC treatment.
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