Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2.
To investigate the function of microRNA-31 (miR-31) in the pathogenesis of gastric cancer (GC) and to explore the possible mechanisms involved in it. A quantitative real-time reverse transcription-PCR (RT-PCR) analysis was performed to evaluate miR-31 expression in GC cell lines. After transfecting GC cells with miR-31 precursors, Alamar blue and apoptosis assays were used to measure the respective proliferation and apoptosis rates. SGPP2 and Smad4 expression were determined by real-time RT-PCR and western blot assays after miR-31 transfection. Animal assay was used to further investigate miR-31 in the pathogenesis of GC. miR-31 was significantly reduced in GC tissues and GC cell lines, and that the reduced miR-31 was associated with distant metastasis and GC clinical pathological stages, miR-31 was lower at stages III/IV than that at stage II. SGPP2 and Smad4 were proven to be the direct target of miR-31. SGPP2 and Smad4 at mRNA and protein levels were negatively correlated with miR-31 in human GC tissues and cancer cell lines. Increased miR-31 significantly repressed SGPP2 and Smad4 at transcriptional and translational levels. Functional studies showed that increasing miR-31 inhibited GC cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of STAT3. In vivo, miR-31 inhibited GC cell growth in tumor-bearing mice. This study has revealed miR-31 as a tumor suppressor and has identified SGPP2 and Smad4 as novel targets of miR-31, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in GC. Therefore, miR-31 could be a useful biomarker for monitoring GC development and progression, and also could have a therapeutic potential by targeting SGPP2, Smad4 and STAT3 for GC therapy.
General Surgery of First Renmin Hospital of Shangqiu, Zhengzhou, China.
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W
Ruoming
Gastrointestinal Surgery of First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Y
Y
Zhen
Cancer Department of First Renmin Hospital of Shangqiu, Zhengzhou, China.
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Z
Tengteng
General Surgery of First Renmin Hospital of Shangqiu, Zhengzhou, China.
H
H
Jisheng
D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014162:Transfection; D019076:Transgenes
C534612:MIRN31 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C539917:Mirn31 microRNA, mouse; D051901:Smad4 Protein; C498526:SGPP2 protein, human; D010744:Phosphoric Monoester Hydrolases