The Expression Of RNA-binding Protein RNPC1 Decreased In Renal Cell Carcinoma And Represses Renal Cancer Cell Proliferation,migration,and Invasion

Objective:The objective of this study was to investigate the role of RNPC1 in the development of renal cell carcinoma(RCC).Method:In this study,we detected the expression of RNPC1 mRNA and RNPC1 protein in RCC cells used qRT-PCR and Western blot(WB).We detected the change of protein expression and mRNA of RNPC1 after transfection with RNPC1 knockdown or overexpress plasmids in RCC cells.Then we investigated the effects of RNPC1 by cck8,cell proliferation,colony formation assay,migration,invasion and cell cycle assay.Moreover we explored the molecular mechanism of RNPC1 on the biological function of RCC cells.These results were confirmed by western blot in protein level of EMT pathways.Furthermore,xenograft studies using nude mice in vivo were performed.Finally,immunohistochemistry was performed in a tissue microarray of 140 cases to explore the expression of RNPC1 and conduct survival analysis with prognosis of patients.Results:We found that the expression of RNPCI was lower-expressed in RCC cell l ines(p<0.05),Overexpression of RNPC1 could reduce,whereas knockdown of RNPCI could accelerate proliferation of RCC cells.RNPC1 inhibited migration and invasion of RCC cells through EMT suppression by up-regulating E-cadherin and down-regulating p-catenin and vimentin(p<0.05).Moreover,after knock-down of RNPC1,the proportion of G0/G1 in cell cycle was significantly reduced,and corresponding proportion of S and G2/M was improved.And after over-expression of RNPC1,the proportion was in the contrary.Furthermore,above results were further confirmed through tumorigenesis in nude mice.Besides,among the 140 cases,compared with the RNPC1-negative group,it was demonstrated that the RNPC1 expression was associated with Age(p=0.004)and diabetes mellitus patients(p=0.002).However,RNPC1 expression was not associated with other parameters including gender(p=0.939),tumor size(p=0.466),histological grade(p=0.462),and tumor stage(p=0.793).Moreover,Kaplan-Meier analysis showed that renal cell carcinoma patients with lower expression of RNPC 1 had a significantly shorter survival time than those with higher expression of RNPC1(p=0.028).In univariate analysis,histological grade(0.002),tumor stage(0.006),and RNPC1 expression level(0.006)were significantly correlated with the survival rate in patients with RCC(p<0.05).A multivariate analysis showed that histological grade(0.004),tumor stage(0.014),and relative expression of RNPC 1(0.023)were independent prognostic markers for survival of RCC patients.Conclusions:RNPC1 acts as a tumor suppressor in RCC,which has the potential for the prediction of RCC prognosis.