Abstract: Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4  is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4  regulator. In this study, we investigated the expression of CRMP4  and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4  by dual-luciferase reporter assay. We also evaluated the biological roles of miR-130a and CRMP4  in gastric cancer cells by flow cytometry, MTT assay, soft agar colony formation assay, and Transwell tests and confirmed CRMP4  function in vivo, using a tumor xenograft model. Our results demonstrated that CRMP4  expression was significantly decreased at both the gene and protein levels, while miR-130a expression was notably increased, in five human gastric cancer cell lines compared with human gastric epithelial cells. Dual-luciferase reporter assays indicated that CRMP4  was the direct target of miR-130a. Moreover, an inverse regulatory relationship between miR-130a and CRMP4  was verified by qRT-PCR and WB, and overexpression of miR-130a in BGC823 cells enhanced apoptosis and cell proliferation, arrested the cell cycle in G0/G1, and facilitated cell colony formation, invasion, migration, and adhesion, while upregulation of CRMP4  had opposite effects. Finally, the growth and weight of transplanted tumors derived from BGC823 cells in which CRMP4  was knocked down were remarkably reduced. These data indicate that miR-130a is an oncomir targeting CRMP4  and could be developed as a potential prognostic factor and a novel therapeutic target in gastric cancer.
Keywords: gastric cancer, microRNA-130a, miR-130a, CRMP4