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RBM19通过SNHG21/PIM1轴在多西他赛治疗下促进前列腺癌进展。

RBM19 promotes the progression of prostate cancer under docetaxel treatment via SNHG21/PIM1 axis.

作者信息

Zhuang Wei, Xu Siwei, He Qingliu, Su Qingfu, Chen Heyi, Chen Jiabi, Huang Congming, You Zhijiao

机构信息

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, 362000, Quanzhou, Fujian, China.

Department of Dentistry, The Second Affiliated Hospital of Fujian Medical University, Zhongshan North Road Licheng District, 362000, Quanzhou, Fujian, China.

出版信息

Cell Biol Toxicol. 2024 Dec 27;41(1):19. doi: 10.1007/s10565-024-09985-z.

Abstract

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.

摘要

RBM家族蛋白在众多肿瘤的进展中起关键作用。然而,RBM家族蛋白是否参与前列腺癌(PCa)的进展仍有待阐明。在我们的研究中,应用了一个包含针对RBM家族54个成员的shRNA文库的RNAi筛选,以鉴定在多西他赛治疗下参与前列腺癌进展的关键RBM蛋白,并选择了RBM19。RBM19在PCa标本中上调,且与PCa患者的预后和Gleason评分相关。功能分析表明,RBM19在多西他赛治疗下在体内和体外均促进PCa进展。机制上,RBM19可与LncRNA SNHG21结合,从而通过增强其稳定性来增加SNHG21的表达。此外,SNHG21与PIM1蛋白结合并阻止其通过泛素-蛋白酶依赖性降解,最终增强线粒体稳态。总体而言,我们的研究表明RBM19/SNHG21/PIM1轴可能是多西他赛耐受性PCa治疗的有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/11680647/f94b8140f86f/10565_2024_9985_Fig1_HTML.jpg

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