Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer
Weiwei Zhou#, Qiuling Jie#, Tao Pan#, Jingyi Shi, Tiantongfei Jiang, Ya Zhang, Na Ding, Juan Xu*, Yanlin Ma* and Yongsheng Li*.
RNA-binding proteins (RBPs) are key players of gene expression and perturbation of RBP-RNA regulatory network has been observed in various cancer types. Here, we propose a computational method, RBPreg, to identify the RBP regulators by integration of single cell RNA-Seq (N=233,591) and RBP binding data. Pan-cancer analyses suggest that RBP regulators exhibit cancer and cell specificity and perturbation of RBP regulatory network is involved in cancer hallmark-related functions. We prioritize an oncogenic RBP-HNRNPK, which is highly expressed in tumors and associated with poor prognosis of patients. Functional assays performed in cancer cells reveal that HNRNPK promotes cancer cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic investigations further demonstrate that HNRNPK promotes tumorigenesis and progression by directly binding to MYC and perturbed the MYC targets pathway in lung cancer. Our results provide a valuable resource for characterizing RBP regulatory networks in cancer, yielding potential biomarkers for precision medicine.
A web server was further set up for facilitating the identification of RBP regulators: http://bio-bigdata.hrbmu.edu.cn/RBPreg/