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Mechanism of microRNA-152-3p-Mediated Regulation of Autophagy and Sensitivity in Paclitaxel-Resistant Ovarian Cancer

Di Wu1, Yang Zhang1, Luna Zhang1

  • 1Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116027, People's Republic of China.

Oncotargets and Therapy
|February 10, 2025
PubMed
Abstract

Insights

microRNA-152-3p downregulation reverses paclitaxel resistance in ovarian cancer by inhibiting autophagy and downregulating PTEN. This suggests PTEN as a therapeutic target for paclitaxel-resistant ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ovarian cancer remains a leading cause of cancer-related mortality.
  • Paclitaxel resistance is a major clinical challenge in ovarian cancer treatment.
  • MicroRNAs play crucial roles in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the role of microRNA-152-3p in paclitaxel-resistant ovarian cancer cells.
  • To elucidate the underlying mechanisms, including autophagy and PTEN regulation.
  • To explore the therapeutic potential of targeting miR-152-3p or its downstream effectors.

Main Methods:

  • Transfection of miR-152-3p mimics and inhibitors in ovarian cancer cell lines (A2780 and A2780T).
  • Quantitative PCR (qPCR) to assess miRNA and mRNA expression levels.
  • MTT assays to evaluate cell proliferation and drug sensitivity (IC50).
  • Western blotting to detect protein expression of PTEN and ATG4D.

Main Results:

  • miR-152-3p expression was significantly higher in paclitaxel-resistant cells (A2780T) compared to sensitive cells (A2780).
  • Downregulation of miR-152-3p reversed paclitaxel-induced autophagy, inhibited cell proliferation, promoted apoptosis, and reduced drug resistance.
  • Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152-3p, and its downregulation by miR-152-3p was crucial for sensitizing cells to paclitaxel.

Conclusions:

  • miR-152-3p plays a critical role in modulating autophagy and paclitaxel sensitivity in ovarian cancer.
  • PTEN is a key mediator of miR-152-3p's effects on paclitaxel resistance.
  • PTEN represents a promising therapeutic target for overcoming paclitaxel resistance in ovarian cancer, offering a potential translational strategy.
Keywords:
PTENautophagymicroRNA-152-3povarian cancerpaclitaxel resistance

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