ARPC1A is regulated by STAT3 to inhibit ferroptosis and promote prostate cancer progression

Hum Cell. 2022 Sep;35(5):1591-1601. doi: 10.1007/s13577-022-00754-w. Epub 2022 Jul 23.

Abstract

The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT-qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.

Keywords: ARPC1A; Ferroptosis; Prognosis; Prostate cancer; STAT3.

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Cell Line, Tumor
  • Ferroptosis*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Prostate / metabolism
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • STAT3 Transcription Factor* / genetics
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction

Substances

  • ARPC1A protein, human
  • Actin-Related Protein 2-3 Complex
  • STAT3 Transcription Factor
  • STAT3 protein, human