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

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.

Keywords: PIM1; Prostate cancer; RBM19; SNHG21.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Disease Progression
  • Docetaxel* / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-pim-1* / genetics
  • Proto-Oncogene Proteins c-pim-1* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • Docetaxel
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-pim-1
  • RNA-Binding Proteins
  • PIM1 protein, human
  • Antineoplastic Agents