MiR-208a enhances cell proliferation and invasion of gastric cancer by targeting SFRP1 and negatively regulating MEG3

• Published in: The international journal of biochemistry & cell biology Vol. 102; pp. 31 - 39
• Main Authors: Cui, Hai-Bin, Ge, Huai-E, Wang, Yong-Sen, Bai, Xi-Yong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2018
• Subjects: Base Sequence; Cell Proliferation - genetics; Female; Gastric cancer; Humans; Intercellular Signaling Peptides and Proteins - genetics; Male; MEG3; Membrane Proteins - genetics; MicroRNAs - genetics; Middle Aged; MiR-208a; Neoplasm Invasiveness; Prognosis; RNA, Long Noncoding - genetics; SFRP1; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Up-Regulation - genetics; MEG3; MiR-208a; SFRP1; Prognosis; Gastric cancer
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2018.06.004

•MiR-208a expression is significantly increased in GC tissues and positively associates with shorter overall survival (OS) time of GC.•MiR-208a promotes cell proliferation and invasion abilities of GC.•MiR-208a enhances cell proliferation and invasion of gastric cancer by targeting SFRP1 and negatively regulating MEG3. 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.