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MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer

K J Sindhu1, Venkatesan Nalini1, G K Suraishkumar1

  • 1Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India.

Translational Oncology
|August 2, 2024
PubMed
Abstract

Insights

MicroRNA-34b (miR-34b) induces cellular senescence and oxidative stress in cervical cancer by targeting TWIST1. This finding offers a potential therapeutic strategy for cervical cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cervical cancer progression involves complex molecular mechanisms.
  • MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
  • Identifying novel therapeutic targets is essential for effective cervical cancer treatment.

Purpose of the Study:

  • To elucidate the role of miR-34b in cervical cancer progression.
  • To investigate the mechanism of miR-34b-mediated tumor suppression.
  • To evaluate miR-34b as a potential therapeutic target, possibly in combination therapy.

Main Methods:

  • Ectopic expression of miR-34b in cervical cancer cell lines using a tetracycline-inducible system.
  • Assessment of cell viability, apoptosis, senescence, DNA damage, and oxidative stress using various assays (MTT, acridine orange/ethidium bromide staining, SA-β-gal assay, γH2AX foci staining, western blotting, ROS detection).
  • Target validation through TWIST1 knockdown and analysis of miR-34b targetome.

Main Results:

  • Ectopic miR-34b expression induced cellular senescence and increased oxidative stress (ROS) in cervical cancer cells, without significant apoptosis induction.
  • MiR-34b targets TWIST1, an oncogene and EMT regulator, mediating its tumor-suppressive effects.
  • TWIST1 was identified as a significant target of miR-34b, and RITA was identified as a potential senolytic agent for combination therapy.

Conclusions:

  • MiR-34b promotes cellular senescence and oxidative stress by targeting TWIST1 in cervical cancer.
  • The study provides mechanistic insights into miR-34b-mediated tumor suppression.
  • MiR-34b represents a potential therapeutic target for novel combination therapies in cervical cancer.
Keywords:
Cervical cancerMiR-34bOxidative stressSenescenceTWIST1

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