J Cancer 2018; 9(23):4363-4373. doi:10.7150/jca.27533
Promotion of Cell Proliferation through Inhibition of Cell Autophagy Signalling Pathway by Rab3IP is Restrained by MicroRNA-532-3p in Gastric Cancer
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou 510515, China
# co-first authors
Guo W, Chen Z, Chen Z, Yu J, Liu H, Li T, Lin T, Chen H, Zhao M, Li G, Hu Y. Promotion of Cell Proliferation through Inhibition of Cell Autophagy Signalling Pathway by Rab3IP is Restrained by MicroRNA-532-3p in Gastric Cancer. J Cancer 2018; 9(23):4363-4373. doi:10.7150/jca.27533. Available from http://www.jcancer.org/v09p4363.htm
Background: RAB3A-interacting protein (Rab3IP) is known to be involved in cancer; however, its function during the proliferation of gastric cancer (GC) cells remains unknown. Therefore, this study aimed to explore the potential function of Rab3IP in GC.
Methods: The expression of Rab3IP and its clinical pathology value were determined by quantitative real-time PCR and immunohistochemistry. Rab3IP (knockdown and overexpression) and light chain 3 (LC3) lentiviruses were transfected into GC cells, and cell proliferation was measured using cell counting kit-8, plate clone formation, flow cytometry, and tumorigenesis assays. Cell autophagy was measured using a confocal laser scanning microscope and by western blotting. Luciferase reporter assay was performed to analyse the regulation of Rab3IP by microRNA-532-3p (miR-532-3p).
Results: Overexpression of Rab3IP in GC samples enhanced the cell proliferation ability, but decreased the number of autophagosomes and expression of LC3-II and sequestosome-1 (SQSTM1 or p62) markers. Furthermore, we found that miR-532-3p can bind to the 3ʹUTR region of RAB3IP and inhibit the proliferation ability of GC cells. Further, the expression of miR-532-3p negatively correlated with that of Rab3IP.
Conclusions: Our study elucidates the central role of Rab3IP in inducing proliferation of GC cells through its involvement in autophagy. miR-532-3p directly targets Rab3IP and represses its function, thereby demonstrating a novel regulatory link in GC.
Keywords: Rab3IP, miR-532-3p, cell proliferation, cell autophagy, gastric cancer