Polypyrimidine Tract-Binding Protein 1 promotes proliferation, migration and invasion in clear-cell renal cell carcinoma by regulating alternative splicing of PKM.
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 cellsin 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 cellsin 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.
Department of Laboratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Junyi
J
Jiang
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Xu
X
Chen
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Hao
H
Liu
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Jing
J
Shao
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Ruihui
R
Xie
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Peng
P
Gu
Department of Laboratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhou, China.
Chaohui
C
Duan
PKM2; PTBP1; metastasis; proliferation; renal cell carcinoma