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

Chen,Yiming; Zhou,Bin; Xu,Lubai; Fan,Hengwei; Xie,Junqin; Wang,Dan

doi:10.3892/mmr.2017.6640

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

Authors:
- Yiming Chen
- Bin Zhou
- Lubai Xu
- Hengwei Fan
- Junqin Xie
- Dan Wang
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Affiliations: Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 29, 2017 https://doi.org/10.3892/mmr.2017.6640
Pages: 755-763
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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