RNA-binding protein IGF2BP2 suppresses metastasis of clear cell renal cell carcinoma by enhancing CKB mRNA stability and expression

RNA 结合蛋白 IGF2BP2 通过增强 CKB mRNA 稳定性和表达来抑制透明细胞肾细胞癌的转移

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作者:Junwu Ren, Bo Huang, Wei Li, Yongquan Wang, Xiaojuan Pan, Qiang Ma, Yuying Liu, Xiaolin Wang, Ce Liang, Yuying Zhang, Shimin Wang, Feifei Yang, Haiping Li, Hao Ning, Yan Jiang, Changhong Qin, Ai Ran, Bin Xiao

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with a highly aggressive phenotype and poor prognosis. RNA binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation and have been implicated in tumorigenesis. RBPs have the potential to become a new therapeutic target for ccRCC. In this study, we screened and validated that insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) as an RBP, was down-regulated in ccRCC tissues and cell lines. Functionally, we verified that IGF2BP2 significantly suppressed the migration and invasion ability of ccRCC in vitro and in vivo. Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.

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