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MiR-335-5p restores cisplatin sensitivity in ovarian cancer cells through targeting BCL2L2

Ruonan Liu1, Hailong Guo2, Shifen Lu3

  • 1Department of Gynecological, Affiliated Tumor Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou, China.

Cancer Medicine
|July 19, 2018
PubMed
Abstract

Insights

MicroRNA miR-335-5p is downregulated in cisplatin-resistant ovarian cancer. Upregulating miR-335-5p enhances cisplatin sensitivity by targeting BCL2L2, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cisplatin resistance is a major challenge in ovarian cancer treatment.
  • MicroRNAs (miRNAs) play crucial roles in cancer progression and drug resistance.
  • The specific role of miR-335-5p in cisplatin-resistant ovarian cancer remains to be fully elucidated.

Purpose of the Study:

  • To investigate the association between miR-335-5p and BCL2L2.
  • To explore the influence of the miR-335-5p/BCL2L2 axis on cisplatin-resistant ovarian cancer cells.
  • To determine the therapeutic potential of targeting this axis.

Main Methods:

  • Microarray analysis to identify differentially expressed miRNAs in cisplatin-resistant cells.
  • Cell function experiments to assess the impact of miR-335-5p on cisplatin sensitivity.
  • Luciferase assay to validate the targeting relationship between BCL2L2 mRNA and miR-335-5p.
  • Tumor xenograft models to confirm in vivo function.

Main Results:

  • MiR-335-5p was found to be lowly expressed in cisplatin-resistant ovarian cancer cells.
  • Overexpression of miR-335-5p significantly reduced cell survival and promoted apoptosis induced by cisplatin.
  • BCL2L2 was confirmed as a direct target of miR-335-5p, and its silencing mimicked the effects of miR-335-5p overexpression.
  • In vivo studies confirmed miR-335-5p's role in restoring cisplatin sensitivity.

Conclusions:

  • Upregulation of miR-335-5p enhances cisplatin sensitivity in ovarian cancer by suppressing BCL2L2.
  • The miR-335-5p/BCL2L2 axis represents a promising therapeutic target for overcoming cisplatin resistance in ovarian cancer patients.
  • Further clinical investigation of miR-335-5p as a therapeutic agent is warranted.
Keywords:
BCL2L2cisplatinmiR-335-5povarian cancer

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