Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis

MicroRNAs (miRNAs) have emerged as important gene regulators and are recognizedas oncogenes or tumor suppressor genes in carcinogenesis. Gastric cancer is oneof the most common malignant diseases worldwide. Our previous studies have revealedthat miR-146a is upregulated in gastric epithelial cells infected with Helicobacterpylori (H. pylori) and in mucosal tissues from H. pylori-positive patients. However,the role of miR-146a in gastric cancer is largely unknown. In the current study,we showed that miR-146a was upregulated in 20 gastric cancer tissues comparedwith matched non-tumor adjacent tissues by quantitative RT-PCR. Furthermore, ectopicexpression of miR-146a could improve cell proliferation in vitro by using CellCounting kit 8 (CCK-8). We also found that miR-146a inhibited apoptosis of gastriccancer cells by flow cytometry (FCM) and Caspase-Glo® 3/7 assay. Using targetprediction algorithms, luciferase reporter assay and Western blot assay, SMADfamily member 4 (SMAD4) was identified as a target gene of miR-146a in gastriccancer. Moreover, an inverse correlation was observed between the expression ofSMAD4 mRNA and miR-146a in gastric cancer tissues (R=-0.731, P=0.039, Pearson'scorrelation). Taken together, our results provide important evidence that miR-146acan directly target SMAD4, and suggest that miR-146a may play a role in the developmentof gastric cancer by modulating cell proliferation and apoptosis. miR-146a couldserve as a potential biomarker and therapeutic target against gastric cancer.