High expression of MRPL13 promotes cell cycle progression and proliferation of gastric cancer cells by inhibiting p53 signaling to affect long-term prognosis

Abstract

To determine the expression of mitochondrial ribosomal protein L13 (MRPL13) in gastric cancer and its impact on long-term prognosis and explore the possible mechanism. We analyzed MRPL13 expression level in gastric cancer and its association with the patients' prognosis based on the public cancer database the data of 100 gastric cancer patients undergoing radical gastrectomy in our hospital from January, 2014 to October, 2017. We further assessed the effects of MRPL13 overexpression and knockdown on proliferation and cell cycle of gastric cancer MGC-803 and SGC-7901 cells in vitro and on subcutaneous xenograft growth in nude mice. Both bioinformatic analysis and the patients' data demonstrated that the expression level of MRPL13 was significantly higher in gastric cancer than in adjacent tissues (P<0.05) and positively correlated with peripheral blood Ki67, CEA and CA19-9 levels (P<0.05). High expression of MRPL13 was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 3.284; 95% CI: 1.537-7.016). Gene set enrichment analysis suggested that MRPL13 was involved in cell cycle and p53 signaling. In cultured gastric cancer cells, MRPL13 overexpression significantly promoted cell proliferation, G1/S phase transition and the expressions of cyclin D1 and CDK6 (P<0.05), and MRPL13 knockdown produced the opposite effects (P<0.05). MRPL13 overexpression significantly promoted gastric cancer cell xenograft growth (P<0.05), and MRPL13 knockdown obviously inhibited tumor growth in nude mice (P<0.05). In both cultured gastric cancer cells and the xenografts in nude mice, MRPL13 overexpression significantly decreased while MRPL13 knockdown enhanced the expressions of p53 and p21 (P<0.05). MRPL13 is highly expressed in gastric cancer and affects the long- term prognosis of the patients possibly by inhibiting p53 signaling to promote cancer cell proliferation and cell cycle progression.