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 recognized             as oncogenes or tumor suppressor genes in carcinogenesis. Gastric cancer is one             of the most common malignant diseases worldwide. Our previous studies have revealed             that miR-146a is upregulated in gastric epithelial cells infected with Helicobacter             pylori (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 compared             with matched non-tumor adjacent tissues by quantitative RT-PCR. Furthermore, ectopic             expression of miR-146a could improve cell proliferation in vitro by using Cell             Counting kit 8 (CCK-8). We also found that miR-146a inhibited apoptosis of gastric             cancer cells by flow cytometry (FCM) and Caspase-Glo® 3/7 assay. Using target             prediction algorithms, luciferase reporter assay and Western blot assay, SMAD             family member 4 (SMAD4) was identified as a target gene of miR-146a in gastric             cancer. Moreover, an inverse correlation was observed between the expression of             SMAD4 mRNA and miR-146a in gastric cancer tissues (R=-0.731, P=0.039, Pearson's             correlation). Taken together, our results provide important evidence that miR-146a             can directly target SMAD4, and suggest that miR-146a may play a role in the development             of gastric cancer by modulating cell proliferation and apoptosis. miR-146a could             serve as a potential biomarker and therapeutic target against gastric cancer.
Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, and Department of Pharmacy, Southwest Hospital, Chongqing 400038, PR China.
Bin
B
Xiao
En-Dong
ED
Zhu
Na
N
Li
Dong-Shui
DS
Lu
Wei
W
Li
Bo-Sheng
BS
Li
Yong-Liang
YL
Zhao
Xu-Hu
XH
Mao
Gang
G
Guo
Pei-Wu
PW
Yu
Quan-Ming
QM
Zou
D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D016481:Helicobacter Infections / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051901:Smad4 Protein / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D051901:Smad4 Protein