MicroRNA-495 Inhibits Gastric Cancer Cell Migration and Invasion Possibly via Targeting High Mobility Group AT-Hook 2 (HMGA2).
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.
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Huashe
H
Wang
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Zhipeng
Z
Jiang
Department of Digestive Endoscopic Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Honglei
H
Chen
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Xiaobin
X
Wu
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Jun
J
Xiang
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
Junsheng
J
Peng
D024761:AT-Hook Motifs; D000199:Actins / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D025743:HMGA2 Protein; C577768:MIRN495 microRNA, human; D035683:MicroRNAs; D014746:Vimentin