The present studies have identified that microRNAs function as regulators in different diseases including cancers. However, the expression patterns and underlying molecular mechanisms of miR-208a involved in gastric cancer (GC) remain little known. In the study, our results demonstrated that miR-208a expression was significantly increased in GC tissues compared with adjacent normal tissues by performing qRT-PCR. Higher miR-208a expression was association with lymph node metastasis and TNM stage in GC patients. Kaplan-Meier analysis verified that patients with higher miR-208a expression were significantly associated with shorter overall survival (OS) time. Univariate and multivariate Cox analysis revealed that lymph node metastasis, TNM stage and higher miR-208a were independent risks factors of OS time. Ectopic expression of miR-208a by treatment with miR-208a mimic promoted cell proliferation and invasion abilities, but downregulation of miR-208a by treatment with miR-208a inhibitor had an opposite effects. Furthermore, we identified specific targeting sites for miR-208a in the 3'-untranslated region (3'-UTR) of the SFRP1 gene by dual-luciferase reporter assay. Upregulation of MiR-208a promoted cell proliferation and invasion by suppressing SFRP1 expression in GC cells. Moreover, dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and qRT-PCR analysis demonstrated that miR-208a targeted MEG3 and negatively regulated MEG3 expression in GC cells. Thus, these data indicated that miR-208a promoted GC progression by targeting SFRP1 and negatively regulating MEG3, which may be a potential therapeutic target of GC.
Keywords: Gastric cancer; MEG3; MiR-208a; Prognosis; SFRP1.
Copyright © 2018. Published by Elsevier Ltd.