SF3B4 Regulates Cellular Senescence and Suppresses Therapy-induced Senescence of Cancer Cells

Seungyeon Yang1,2, Minbeom Ko1,2, Soojung Claire Hur3

  • 1Department of Biochemistry, Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

PubMed
Abstract

Insights

Splicing factor SF3B4 regulates cellular senescence. Its reduction induces senescence, while its overexpression mitigates therapy-induced senescence (TIS) in cancer cells, suggesting SF3B4 as a therapeutic target for cancer treatment.

Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • Cellular senescence is a permanent cell cycle exit that prevents tumor growth but contributes to aging and inflammation.
  • Therapy-induced senescence (TIS) halts cancer cell proliferation and metastasis, offering a therapeutic strategy with minimized cytotoxicity.
  • Understanding the regulators of senescence is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To investigate the role of splicing factor 3B subunit 4 (SF3B4) in regulating cellular senescence.
  • To determine the involvement of SF3B4 in therapy-induced senescence (TIS) in cancer cells.
  • To explore SF3B4 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Senescence induction was assessed using beta-galactosidase staining.
  • SF3B4 and p21 expression levels were quantified via RT-qPCR and western blotting.
  • Cell proliferation and cell death assays were performed to evaluate functional outcomes.

Main Results:

  • SF3B4 expression was found to decrease in senescent human fibroblasts.
  • Knockdown of SF3B4 induced senescence through a p21-dependent pathway in both fibroblasts and A549 non-small cell lung cancer (NSCLC) cells.
  • Overexpression of SF3B4 attenuated doxorubicin-induced senescence in A549 NSCLC cells.

Conclusions:

  • SF3B4 plays a significant role in regulating cellular senescence.
  • The findings suggest SF3B4 as a potential therapeutic target for enhancing cancer treatment efficacy through TIS.
  • Targeting SF3B4 could offer a novel strategy to suppress tumor growth and improve treatment outcomes.

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