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Related Experiment Video

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MiR-138 Suppresses the PDK1 Expression to Decrease the Oxaliplatin Resistance of Colorectal Cancer.

Yao Wang1, Duo Zhang1, Yao Li1

  • 1Inspection Institute, Jilin Medical University, Jilin City, Jilin Province 132013, People's Republic of China.

Oncotargets and Therapy
|May 21, 2020
PubMed
Summary

Overexpression of miR-138 combats oxaliplatin resistance in colorectal cancer (CRC) by inhibiting PDK1. This strategy enhances oxaliplatin

Keywords:
PDK1colorectal cancermiR-138oxaliplatin

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxaliplatin is a key platinum-based chemotherapy for colorectal cancer (CRC).
  • Acquired drug resistance limits oxaliplatin efficacy in CRC treatment.
  • Strategies to overcome oxaliplatin resistance are crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of miR-138 in oxaliplatin resistance in colorectal cancer cells.
  • To elucidate the molecular mechanisms by which miR-138 affects oxaliplatin sensitivity.
  • To explore miR-138 as a potential therapeutic target for overcoming oxaliplatin resistance in CRC.

Main Methods:

  • Established oxaliplatin-resistant colorectal cancer cell lines (HT29/R, SW480/R).
  • Assessed glycolysis (glucose consumption, lactate generation, LDH activity) and oxygen consumption rate (OCR).
  • Utilized MTT assays, qRT-PCR, Western blot, and dual-luciferase reporter assays to confirm miR-138 targeting of PDK1.
  • Measured reactive oxygen species (ROS) levels via flow cytometry.

Main Results:

  • Resistant cells showed increased glycolysis and decreased OCR compared to parental cells.
  • miR-138 overexpression enhanced oxaliplatin-induced cytotoxicity in resistant cells.
  • miR-138 directly targets and inhibits PDK1 expression, leading to increased OCR.
  • Overexpression of miR-138 increased ROS production and promoted apoptosis in oxaliplatin-treated resistant cells.

Conclusions:

  • miR-138 overexpression suppresses PDK1 expression, thereby reducing oxaliplatin resistance in colorectal cancer.
  • Targeting the miR-138/PDK1 pathway offers a promising strategy to re-sensitize CRC to oxaliplatin therapy.
  • Modulating miR-138 levels may represent a novel therapeutic approach for managing oxaliplatin-resistant colorectal cancer.