Genome-wide screening for the G-protein-coupled receptor (GPCR) pathway-related therapeutic gene RGS19 (regulator of G protein signaling 19) in bladder cancer

Bioengineered. 2021 Dec;12(1):5892-5903. doi: 10.1080/21655979.2021.1971035.

Abstract

Bladder cancer is one of the most severe genitourinary cancers, causing high morbidity worldwide. However, the underlying molecular mechanism is not clear, and it is urgent to find target genes for treatment. G-protein-coupled receptors are currently a target of high interest for drug design. Thus, we aimed to identify a target gene-related to G-protein-coupled receptors for therapy. We used The Cancer Genome Atlas (TCGA) and DepMap databases to obtain the expression and clinical data of RGS19. The results showed that RGS19 was overexpressed in a wide range of tumor, especially bladder cancer. We also explored its effect on various types of cancer. High expression of RGS19 was also shown to be significantly associated with poor prognosis. Cell models were constructed for cell cycle detection. shRGS19 can halt the cell cycle at a polyploid point. RGS19 is a G-protein-coupled receptor signaling pathway-related gene with a significant effect on survival. We chose RGS19 as a therapeutic target gene in bladder cancer. The drug GSK1070916 was found to inhibit the effect of RGS19 via cell rescue experiments in vitro.

Keywords: Bladder cancer; cell cycle; g-protein-coupled receptor; gsk1070916; rgs19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Databases, Genetic
  • Humans
  • Indoles / pharmacology
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • RGS Proteins* / antagonists & inhibitors
  • RGS Proteins* / genetics
  • RGS Proteins* / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism

Substances

  • Aza Compounds
  • GSK 1070916
  • Indoles
  • Protein Kinase Inhibitors
  • RGS Proteins
  • regulator of G-protein signalling 19

Grants and funding

National Natural Science Foundation of China (No. 82060465 to L.X.), Natural Science Foundation of Jiangxi Province (No. 20161BAB205258. to L.X.), and Science and Technology Support Program of Education Department of Jiangxi Province (No. GJJ150052 to L.X.).