RNA Binding Protein RNPC1 Promotes Gastric Cancer Progression via Stabilizing the Aurora Kinase B mRNA

Abstract

BackgroundRNPC1, was reported to act as a tumor suppressor by binding and regulating the expression of the target genes in various cancers. However, the role of RNPC1 on the gastric cancer and the underly mechanisms were still unclear.MethodsGastric cancer cells were stably transfected with lentivirus. Proliferation, migration, invasion, cell cycle in vitro as well as tumorigenesis in vivo were performed to assess the role of RNPC1. Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the relation between RNPC1 and Aurora kinase B (AURKB). RNA immunoprecipitation(RIP), RNA electrophoretic mobility shift assay (REMSA), dual-luciferase reporter assay were employed to identify the direct binding sites of RNPC1 with AURKB mRNA. CCK-8 assay conducted to confirm the function of AURKB in RNPC1-induced growth promotion. ResultsHigh RNPC1 expression was found in gastric cancer tissues and cell lines, associated with high TNM stage. RNPC1 overexpression could significantly promote the proliferation, migration, invasion of gastric cancer cells. Knockdown of RNPC1 could impede gastric cancer tumorigenesis in nude mice. AURKB expression was positively related with RNPC1. RNPC1 binded to the 3'-untranslated region (3'-UTR) of AURKB directly and enhanced AURKB mRNA stability. AURKB could reversed the proliferation induced by RNPC1 in gastric cancer cells. RNPC1 resulted in mitotic defects, aneuploidy and chromosomal instability in gastric cancer cells, as AURKB did. ConclusionRNPC1 acted as an oncogene in gastric cancer by influencing cell mitosis by regulating AURKB mRNA stability, which may provide a potential biomarker and therapeutic target for gastric cancer.