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PRP4 Induces Epithelial-Mesenchymal Transition and Drug Resistance in Colon Cancer Cells via Activation of p53

Salman Ul Islam1,2, Muhammad Bilal Ahmed2, Jong-Kyung Sonn3

  • 1Department of Pharmacy, Cecos University, Hayatabad, Peshawar 25000, Pakistan.

International Journal of Molecular Sciences
|March 25, 2022
PubMed

Insights

Pre-mRNA processing factor 4B (PRP4) drives cancer progression by inducing drug resistance and epithelial-mesenchymal transition (EMT). PRP4 directly interacts with p53 and upregulates hypoxia-inducible factor 1α (HIF-1α) and miR-210, promoting cancer cell survival.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • Pre-mRNA processing factor 4B (PRP4) is implicated in pre-mRNA splicing and signal transduction.
  • PRP4 influences actin cytoskeleton assembly, epithelial-mesenchymal transition (EMT), and drug resistance in cancer cells.
  • PRP4 possesses kinase-like domains, suggesting a role in protein phosphorylation, including p53.

Purpose of the Study:

  • To investigate the mechanism by which PRP4 induces drug resistance and EMT.
  • To elucidate the role of p53, miR-210, and hypoxia-inducible factor 1α (HIF-1α) in PRP4-mediated cancer progression.

Main Methods:

  • Investigated PRP4's direct binding to p53 and its effect on p53 phosphorylation.
  • Analyzed PRP4-induced miR-210 transcription in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner.
  • Utilized si-miR210 and si-HIF to block or silence specific pathways and observed the effects on EMT and drug resistance.

Main Results:

  • PRP4 directly binds to p53, inducing its phosphorylation and promoting drug resistance and EMT.
  • PRP4 overexpression activates miR-210 transcription via HIF-1α, which in turn activates p53.
  • Inhibition of miR-210 reversed PRP4-induced EMT and cell survival pathways.
  • PRP4-induced EMT and drug resistance are dependent on the sequential activation of HIF-1α, miR-210, and p53.

Conclusions:

  • PRP4 promotes cancer development and progression by directly interacting with p53 and upregulating HIF-1α and miR-210.
  • The findings highlight a novel pathway involving PRP4, p53, HIF-1α, and miR-210 in driving EMT and drug resistance.
  • Targeting PRP4 may offer a therapeutic strategy for colon cancer patients.
Keywords:
EMTHCT116PRP4drug resistancemiR-210p53

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