Wei Zhuang, Siwei Xu, Qingliu He, Qingfu Su, Heyi Chen, Jiabi Chen, Congming Huang, Zhijiao You
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RBM19 promotes the progression of prostate cancer under docetaxel treatment via SNHG21/PIM1 axis.
RBM family proteins plays the critical role in the progression of numerous tumors. However, whether RBM family proteins involved in prostate cancer (PCa) progression is remain elucidated. In our study, an RNAi screen containing shRNA library targeting 54 members of the RBM family was applied to identify the critical RBM proteins involved in prostate cancer progression under docetaxel treatment, and RBM19 was selected. RBM19 was up-regulated in PCa specimens and correlated with the prognosis and Gleason score of PCa patients. Functionally assays revealed that RBM19 promoted PCa progression under docetaxel treatment both in vivo and in vitro. Mechanistically, RBM19 could bind to LncRNA SNHG21, thereby increased SNHG21 expression through enhancing its stability. Furthermore, SNHG21 bind to PIM1 proteins and prevented it from ubiquitin-protease dependent degradation and ultimately enhancing mitochondrial homeostasis. Overall, our study indicates the RBM19/SNHG21/PIM1 axis may be the encouraging target for docetaxel-tolerance PCa treatment.
期刊介绍:
Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.