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MicroRNA-495 Inhibits Gastric Cancer Cell Migration and Invasion Possibly via Targeting High Mobility Group AT-Hook 2 (HMGA2)

Huashe Wang, Zhipeng Jiang, Honglei Chen, Xiaobin Wu, Jun Xiang, Junsheng Peng

(Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland))

Med Sci Monit 2017; 23:640-648

DOI: 10.12659/MSM.898740

Published: 2017-02-04


BACKGROUND: Gastric cancer is one of the most common malignancies, and has a high mortality rate. miR-495 acts as a suppressor in some cancers and HMGA2 (high mobility group AT-hook 2) is a facilitator for cell growth and epithelial-mesenchymal transition (EMT), but little is known about their effect in gastric cancer. This study aimed to investigate the role and mechanism of miR-495 in gastric cancer.
MATERIAL AND METHODS: miR-495 levels were quantitatively analyzed in gastric cancer tissue and GES-1, SGC-7901, BGC-823, and HGC-27 cell lines by qRT-PCR. Levels of miR-495 and HMGA2 were altered by cell transfection, after which cell migration and invasion were examined by Transwell and E-cadherin (CDH1); vimentin (VIM), and alpha smooth muscle actin (ACTA2) were detected by qRT-PCR and Western blotting. The interaction between miR-495 and HMGA2 was verified by dual-luciferase reporter assay.
RESULTS: miR-495 was significantly downregulated in cancer tissue and cell lines (p<0.05). Its overexpression inhibited cell migration and invasion, elevated CDH1, and inhibited VIM and ACTA2 levels in BGC-823 and HGC-27 cells. miR-495 directly inhibited HMGA2, which was upregulated in gastric cancer tissue, and promoted cell migration and invasion, inhibited CDH1, and elevated VIM and ACTA2.
CONCLUSIONS: miR-495 acts as a tumor suppressor in gastric cancer by inhibiting cell migration and invasion, which may be associated with its direct inhibition on HMGA2. These results suggest a promising therapeutic strategy for gastric cancer treatment.

Keywords: Epithelial-mesenchymal transition, HMGA2 Protein, MicroRNAs, Neoplasm Invasiveness, Stomach Neoplasms, Transcellular Cell Migration



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