MicroRNA-186 suppresses cell proliferation and metastasis through targeting MAP3K2 in non-small cell lung cancer
MicroRNA-186 suppresses cell proliferation and metastasis through targeting MAP3K2 in non-small cell lung cancer
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DOI：
10.3892/ijo.2016.3637
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发表时间：
2016-10-01
影响因子：
5.2
通讯作者：
He, Jianxing
中科院分区：
文献类型：
--
作者：
Huang, Tonghai;She, Kelin;He, Jianxing
MicroRNA 是一类小的内源性非编码 RNA，在人类癌症的发生和进展中发挥着至关重要的作用。研究发现 miR-186 在多种人类恶性肿瘤中表达减少，并具有肿瘤抑制因子的功能。然而，miR-186在人非小细胞肺癌（NSCLC）生长和转移中的调节机制仍知之甚少。我们研究了 miR-186 在人类 NSCLC 生长和转移中的作用。在本研究中，我们发现肺癌组织和细胞中miR-186显着减少。此外，miR-186的过度表达抑制肺癌细胞增殖、迁移和侵袭，并诱导细胞凋亡。此外，我们发现肺癌组织中确认丝裂原激活蛋白激酶激酶2（MAP3K2）蛋白增加，并证实MAP3K2是miR-186的靶基因。此外，通过RNA干扰敲低MAP3K2可抑制肺癌细胞的增殖、迁移和侵袭，并在体外促进细胞凋亡。此外，我们观察到MAP3K2的过表达部分逆转了miR-186对A549和HCC827细胞系增殖和转移的抑制作用。综合起来；我们的数据表明，miR-186 至少部分通过抑制 MAP3K2 表达来调节肺癌生长和转移。因此，miR-186-MAP3K2可能代表一种新的、有用的潜在的NSCLC临床治疗和诊断靶点。
MicroRNAs are a class of small endogenous non coding RNAs that play crucial roles in the initiation and progression of human cancers. miR-186 was found decreased in various human malignancies and function as a tumor suppressor. However, the regulating mechanism of miR-186 in growth and metastasis of human non-small cell lung cancer (NSCLC) is still poorly understood. We investigated the role of miR-186 in the growth and metastasis of human NSCLC. In the present study, we found that miR-186 was significantly decreased in lung cancer tissues and cells. Furthermore, overexpression of miR-186 suppressed lung cancer cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, we found that confirmed mitogen-activated protein kinase kinase kinase 2 (MAP3K2) protein was increased in lung cancer tissues and confirmed that MAP3K2 is a target gene of miR-186. In addition, knockdown of MAP3K2 by RNA interference inhibited lung cancer cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, we observed tthat the overexpression of MAP3K2 partially reversed the inhibitory effect of miR-186 on the proliferation and metastasis of A549 and HCC827 cell lines. Taken together; our data indicated that miR-186 regulates lung cancer growth and metastasis through suppressing MAP3K2 expression, at least partly. Therefore, miR-186-MAP3K2 may represent a new and useful potential clinical treatment and diagnosis target for NSCLC.