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

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. Key words: microRNA-146a, transforming growth factor [beta]-activated kinase 1, nuclear factor-[kappa]B, apoptosis, gastric cancer