Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer

Molecular Therapy: Nucleic Acids

Yunpeng Zhang¹  Yongsheng Li²  Xia Li³  Xinhui Li³  Liuxin Chen³  Junyi Li³  Qi Wang³  Zhenghong Chang³  Weiwei Zhou³  Tao Pan⁴  Gang Xu⁴ 

[1] Corresponding author: Xia Li, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.;Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China;College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China;Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China;

关键词: RNA binding protein;    alterative splicing;    regulatory network;    cancer;    therapeutic targets;   

DOI  :  

来源: DOAJ

【 摘 要 】

Alternative splicing (AS) plays an important role in gene regulation, and AS perturbations are frequently observed in cancer. RNA binding protein (RBP) is one of the molecular determinants of AS, and perturbations in RBP-gene network activity are causally associated with cancer development. Here, we performed a systematic analysis to characterize the perturbations in AS events across 18 cancer types. We showed that AS alterations were prevalent in cancer and involved in cancer-related pathways. Given that the extent of AS perturbation was associated with disease severity, we proposed a computational pipeline to identify RBP regulators. Pan-cancer analysis identified a number of conserved RBP regulators, which play important roles in regulating AS of genes involved in cancer hallmark pathways. Our application analysis revealed that the expression of 68 RBP regulators helped in cancer subtyping. Specifically, we identified four subtypes of kidney cancer with differences in cancer hallmark pathway activities and prognosis. Finally, we identified the small molecules that can potentially target the RBP genes and suggested potential candidates for cancer therapy. In summary, our comprehensive AS perturbation landscape analysis identified RBPs as potential therapeutic targets in cancer and provided novel insights into the regulatory functions of RBPs in cancer.

【 授权许可】

Unknown