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MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters

Yang Yang1, Yueyuan Chen2, Jiajia Liu1

  • 1Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province 226001, China.

Stem Cells International
|May 9, 2023
PubMed
Abstract

Insights

MicroRNA-125b-5p enhances osteosarcoma drug sensitivity by inhibiting the STAT3 pathway, which regulates ABC transporters. This finding offers new therapeutic strategies for drug-resistant osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma exhibits poor prognosis due to drug resistance.
  • Understanding resistance mechanisms is crucial for developing effective treatments.
  • The role of miR-125b-5p in osteosarcoma drug resistance remains unclear.

Purpose of the Study:

  • To investigate the effects of miR-125b-5p on drug resistance in osteosarcoma cells.
  • To elucidate the molecular mechanisms underlying miR-125b-5p's role in osteosarcoma.
  • To identify potential therapeutic targets for overcoming drug resistance.

Main Methods:

  • Osteosarcoma-resistant miR-125b-5p was identified using bioinformatics databases.
  • Cell proliferation, migration, invasion, and apoptosis were assessed using CCK8, western blot, and transwell assays.
  • Bioinformatic analysis and binding site validation were employed to identify targeting factors and pathways.

Main Results:

  • Upregulation of miR-125b-5p inhibited osteosarcoma cell proliferation, migration, and invasion while promoting apoptosis.
  • miR-125b-5p was found to restore drug sensitivity in drug-resistant osteosarcoma cells.
  • miR-125b-5p targets the 3'-UTR of signal transducer and activator of transcription 3 (STAT3), inhibiting its expression.

Conclusions:

  • The miR-125b-5p/STAT3 axis plays a critical role in mediating osteosarcoma drug resistance.
  • STAT3 influences drug resistance in osteosarcoma by regulating ABC transporters.
  • Targeting the miR-125b-5p/STAT3 pathway presents a promising strategy for treating drug-resistant osteosarcoma.

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