The RNA-binding protein CSTF2 regulates BAD to inhibit apoptosis in glioblastoma

• Published in: International journal of biological macromolecules Vol. 226; pp. 915 - 926
• Main Authors: Xu, Yang, Yuan, Fanen, Sun, Qian, Zhao, Linyao, Hong, Yu, Tong, Shiao, Qi, Yangzhi, Ye, Liguo, Hu, Ping, Ye, Zhang, Zhang, Si, Liu, Baohui, Chen, Qianxue
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 31.01.2023
• Subjects: Apoptosis; Apoptosis - genetics; BAD; bcl-Associated Death Protein - genetics; bcl-Associated Death Protein - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Cell Line, Tumor; Cell Proliferation - genetics; CSTF2; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Humans; RNA binding protein; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; BAD; RNA binding protein; CSTF2; Glioblastoma; Apoptosis
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.12.044

RNA-binding proteins (RBP) regulate several aspects of co- and post-transcriptional gene expression in cancer cells. CSTF2 is involved in the expression of many cellular mRNAs and involved in the 3′-end cleavage and polyadenylation of pre-mRNAs to terminate transcription. However, the role of CSTF2 in human glioblastoma (GBM) and the underlying mechanisms remain unclear. In the present study, CSTF2 was found to be upregulated in GBM, and its high expression predicted poor prognosis. Knockdown CSTF2 induced GBM cell apoptosis both in vitro and in vivo. Specific mechanism studies showed that CSTF2 unstabilized the mRNA of the BAD protein by shortening its 3’ UTR. Additionally, an increase in the expression level of CSTF2 decreased the expression level of BAD. In conclusion, CSTF2 binds to the mRNA of the BAD protein to shorten its 3’UTR, which negatively affects the BAD mediated apoptosis and promotes GBM cell survival.