miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC
miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC
复制标题
YY1介导的miR-1260b通过靶向SOCS6激活KIT信号传导来调节NSCLC中的细胞增殖和凋亡
DOI：
10.1038/s41419-019-1390-y
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发表时间：
2019-02-08
影响因子：
9
通讯作者：
Chen, Liang
中科院分区：
文献类型：
--
作者：
Xia, Yang;Wei, Ke;Chen, Liang
非小细胞肺癌（non-small cell lung cancer，NSCLC）是最常见的恶性肿瘤之一。miRNA已被鉴定为NSCLC的重要生物标志物和调节剂。然而，miR-1260 b对NSCLC细胞增殖和凋亡的功能贡献尚未研究。在这项研究中，miR-1260 b在NSCLC血浆、组织和细胞系中上调，其高表达与肿瘤大小和进展相关。miR-1260b过表达在功能上促进细胞增殖和细胞周期，相反抑制细胞凋亡和衰老。miR-1260b通过直接结合SOCS6的3 ′-UTR负调控SOCS6的表达。此外，miR-1260 b介导的SOCS6抑制激活了KIT信号传导。此外，YY1是miR-1260b的上游调控因子。这项研究首次阐明了由YY1介导的miR-1260 b通过靶向SOCS6激活KIT信号通路，调节NSCLC细胞增殖和凋亡，是NSCLC潜在的生物标志物和治疗靶点。总之，我们的工作提供了新的见解参与细胞增殖和凋亡的NSCLC的分子机制。
Non-small cell lung cancer (NSCLC) is one of the most common aggressive malignancies. miRNAs have been identified as important biomarkers and regulators of NSCLC. However, the functional contributions of miR-1260b to NSCLC cell proliferation and apoptosis have not been studied. In this study, miR-1260b was upregulated in NSCLC plasma, tissues, and cell lines, and its high expression was correlated with tumor size and progression. Functionally, miR-1260b overexpression promoted cell proliferation and cell cycle, conversely inhibited cell apoptosis and senescence. Mechanically, miR-1260b negatively regulated SOCS6 by directly binding to its 3′-UTR. Furthermore, miR-1260b-mediated suppression of SOCS6 activated KIT signaling. Moreover, YY1 was an upstream regulator of miR-1260b. This study is the first to illustrate that miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate NSCLC cell proliferation and apoptosis, and is a potential biomarker and therapeutic target for NSCLC. In sum, our work provides new insights into the molecular mechanisms of NSCLC involved in cell proliferation and apoptosis.