MicroRNA-146a promotes gastric cancer cell apoptosis by targeting transforming growth factor β-activated kinase 1

被引:18
作者
Chen, Yiming [1 ,2 ]
Zhou, Bin [1 ,2 ]
Xu, Lubai [1 ,2 ]
Fan, Hengwei [1 ,2 ]
Xie, Junqin [1 ,2 ]
Wang, Dan [3 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Wenzhou 325000, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Pediat, Wenzhou 325000, Zhejiang, Peoples R China
关键词
microRNA-146a; transforming growth factor beta-activated kinase 1; nuclear factor-kappa B; apoptosis; gastric cancer; NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; PROSTATE-CANCER; DOWN-REGULATION; EXPRESSION; MIR-146A; METASTASIS; INHIBITION; STATISTICS; SUPPRESSES;
D O I
10.3892/mmr.2017.6640
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 beta-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 kappa B alpha (I kappa B alpha) 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 I kappa B alpha 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-kappa B axis.
引用
收藏
页码:755 / 763
页数:9
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