多嘧啶结合蛋白
基因敲除
癌症研究
细胞生长
选择性拼接
生物
癌变
RNA剪接
肾透明细胞癌
细胞
分子生物学
细胞生物学
癌症
肾细胞癌
细胞培养
信使核糖核酸
医学
核糖核酸
病理
基因
遗传学
作者
Junyi Jiang,Xu Chen,Hao Líu,Jing Shao,Ruihui Xie,Peng Gu,Chaohui Duan
摘要
Polypyrimidine Tract-Binding Protein 1 (PTBP1) is an essential RNA-binding protein that regulates diverse biological events through regulating alternative splice of mRNA. PTBP1 induces cancer-promoting splice variants and is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of PTBP1 in clear-cell renal cell carcinoma (ccRCC) are unclear. We investigated PTBP1 expression in 533 ccRCC patients from TCGA and 30 ccRCC patients by immunohistochemistry, and found that PTBP1 expression levels were significantly increased in ccRCC tissues and that high PTBP1 expression was closely correlated with advanced tumor stage, AJCC stage and poor prognosis. Cell biological assays with siRNA-mediated knockdown and lentivirus vector-mediated over-expression demonstrated that PTBP1 promoted proliferation, migration and invasion in ccRCC cells in vitro. Furthermore, PTBP1 increased the transformation from pyruvate kinase muscle 1 (PKM1) to PKM2. Knockdown of PKM2 mainly abolished PTBP1-induced proliferation, migration and invasion in ccRCC cells in vitro. In conclusion, our study indicates that PTBP1 plays a tumorigenic role in ccRCC by mediating PKM2 alternative splicing and it may be a potential prognostic marker and a promising target for treatment of ccRCC.
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