MicroRNA-146a promotes gastric cancer cell apoptosis by targeting transforming growth factor β-activated kinase 1.
MicroRNA-146a promotes gastric cancer cell apoptosis by targeting transforming growth factor β-activated kinase 1.
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DOI：
10.3892/mmr.2017.6640
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Chen Y;Zhou B;Xu L;Fan H;Xie J;Wang D
越来越多的证据表明microRNA（miR）-146 a在各种癌症中作为癌基因或肿瘤抑制因子发挥作用。然而，miR-146 a在胃癌（GC）中的作用仍有待阐明。本研究探讨miR-146 a在胃癌细胞中的功能。本研究的结果显示，miR-146 a调节GC细胞凋亡。过表达miR-146 a可显著增加SGC-7901细胞的凋亡，而抑制miR-146 a则可保护细胞免于凋亡。胃癌细胞中miR-146 a的表达与转化生长因子β激活激酶1（TAK 1）的表达在mRNA和蛋白水平上呈负相关。此外，小干扰RNA介导的TAK 1沉默增强了GC细胞凋亡，而TAK 1的过表达促进了GC细胞的存活。miR-146 a过表达或TAK 1敲低均导致SGC-7901细胞中κBα抑制因子（IκBα）表达水平显著升高，B细胞淋巴瘤2（Bcl-2）表达水平降低。相比之下，沉默miR-146 a或TAK 1过表达下调IκBα，上调Bcl-2表达水平。因此，本研究结果表明miR-146 a/TAK 1/核因子-κB轴参与了一种新的负反馈机制促进胃癌细胞凋亡。
Accumulating evidence suggests that microRNA (miR)-146a functions as an oncogene or tumor suppressor in various cancers. However, the role of miR-146a in gastric cancer (GC) remains to be elucidated. The present study investigated the function of miR-146a in GC cells. The results of the present study revealed that miR-146a modulates GC cell apoptosis. Overexpression of miR-146a significantly increased apoptosis of SGC-7901 cells, whereas inhibition of miR-146a protected cells from apoptosis. miR-146a expression in GC cells was inversely correlated with transforming growth factor β-activated kinase 1 (TAK1) expression, at the mRNA and protein levels. Furthermore, small interfering RNA-mediated silencing of TAK1 enhanced GC cell apoptosis, whereas overexpression of TAK1 promoted survival of GC cells. Overexpression of miR-146a or knockdown of TAK1 led to a marked increase in inhibitor of κBα (IκBα) and a decrease in B-cell lymphoma 2 (Bcl-2) expression levels in SGC-7901 cells. By contrast, silencing of miR-146a or TAK1 overexpression downregulated IκBα and upregulated Bcl-2 expression levels. Therefore, the results of the present study demonstrated a novel negative feedback mechanism to promote GC cell apoptosis involving the miR-146a/TAK1/nuclear factor-κB axis.