KHSRP modulated cell proliferation and cell cycle via regulating PPP2CA and p27 expression in Wilms tumor

Abstract

Wilms tumor (WT) is the most common renal malignancy in children, and the survival rate of high-risk WT patients was still low despite multimodality therapy. KHSRP, an RNA-binding protein, has been proved to be relative to tumor progression in different kinds of malignancies, but the function of KHSRP in WT remained unclear. Here, our study aimed to explore and clarify the function of KHSRP in WT cells and its molecular mechanism. Thus, our results showed that KHSRP was highly expressed in WT tumor tissues compared to normal kidney tissues and correlated with poor prognosis in WT patients. Downregulation of KHSRP using siRNAs in WT cell line SK-NEP-1 and Wit49 resulted in inhibition of cell proliferation and cell cycle arrest via stabilizing and upregulating p27 protein. Furthermore, mechanistic analyses revealed that KHSRP bound to 3’UTR of PPP2CA mRNA and modulating its mRNA stability, resulting in regulation of the phosphorylation level and protein stability of p27 in WT cell lines. In conclusion, our results demonstrated that KHSRP played an important role in WT and modulated cell proliferation and cell cycle via regulating the expression of PPP2CA and p27.