MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1

Hui Liu1, Xin-Hua Cheng1

  • 1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Oncotarget
|March 20, 2018
PubMed

Insights

MicroRNA-29b (miR-29b) can overcome oxaliplatin resistance in colorectal cancer. Restoring miR-29b levels targets SIRT1, enhancing apoptosis and improving treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oxaliplatin is a key chemotherapy for advanced colorectal cancer.
  • Acquired resistance to oxaliplatin limits its effectiveness.
  • Mechanisms of oxaliplatin resistance require further investigation.

Purpose of the Study:

  • To explore mechanisms of oxaliplatin resistance in colorectal cancer.
  • To investigate the role of miR-29b in oxaliplatin resistance.
  • To identify therapeutic strategies to overcome oxaliplatin resistance.

Main Methods:

  • Established an oxaliplatin-resistant colorectal cancer cell line (OR-SW480).
  • Assessed miR-29b expression levels in resistant cells.
  • Investigated the effect of miR-29b restoration on oxaliplatin sensitivity.
  • Identified SIRT1 as a direct target of miR-29b.
  • Analyzed the SIRT1/ROS/JNK pathway and apoptosis markers.

Main Results:

  • Intracellular miR-29b expression was significantly decreased in OR-SW480 cells.
  • Overexpression of miR-29b resensitized OR-SW480 cells to oxaliplatin.
  • miR-29b directly targets and downregulates SIRT1 expression.
  • miR-29b restoration increased ROS production and JNK phosphorylation.
  • miR-29b promoted apoptosis via caspase activation.

Conclusions:

  • miR-29b plays a crucial role in reversing oxaliplatin resistance in colorectal cancer.
  • The miR-29b/SIRT1/ROS/JNK pathway is a novel mechanism underlying oxaliplatin resistance.
  • Targeting miR-29b offers a potential therapeutic strategy to enhance oxaliplatin efficacy.

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