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

Cheng Cheng; Yuanxia Cai; Xiaowei Liu; Yangkun Wu; Qianqian Cheng; Yeming Wu; Zhixiang Wu

doi:10.1016/j.cellsig.2022.110447

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

Cell Signal. 2022 Dec:100:110447. doi: 10.1016/j.cellsig.2022.110447. Epub 2022 Aug 25.

Authors

Cheng Cheng¹, Yuanxia Cai¹, Xiaowei Liu¹, Yangkun Wu¹, Qianqian Cheng¹, Yeming Wu², Zhixiang Wu³

Affiliations

¹ Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, 200092 Shanghai, China.
² Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, 200092 Shanghai, China; Department of Pediatric Surgery, Hangzhou Children's Hospital, Hangzhou, Hangzhou 310010, China. Electronic address: wuyeming@xinhuamed.com.cn.
³ Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, 200092 Shanghai, China; Department of Pediatric Surgery, Children's Hospital of Soochow University, 215003 Suzhou, China. Electronic address: wuzhixiang@xinhuamed.com.cn.

PMID: 36029941
DOI: 10.1016/j.cellsig.2022.110447

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.

Keywords: Cell cycle; KHSRP; PP2A; Wilms tumor; p27.