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miR-340 alleviates chemoresistance of osteosarcoma cells by targeting ZEB1

Haibin Yan1, Bingyun Zhang, Chongbin Fang

  • 1Department of Orthopedics, the Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, China.

Anti-Cancer Drugs
|March 2, 2018
PubMed

Insights

MicroRNA-340 (miR-340) is downregulated in osteosarcoma (OS) and drug-resistant cells. Restoring miR-340 can overcome chemoresistance by targeting ZEB1, offering a potential therapeutic strategy for resistant osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemoresistance presents a significant clinical challenge in osteosarcoma (OS) treatment.
  • Understanding the molecular mechanisms underlying chemoresistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of microRNA-340 (miR-340) in the chemoresistance of osteosarcoma.
  • To identify the molecular targets and pathways regulated by miR-340 in drug-resistant OS cells.

Main Methods:

  • Utilized plasmid construction, transfection, miRNA arrays, PCR, and Western blot analysis.
  • Performed MTT, apoptosis, and luciferase assays in MG-63 and MG-63/cisplatin-resistant cells.
  • Analyzed miR-340 and ZEB1 expression in OS tissues and cell lines.

Main Results:

  • miR-340 was found to be downregulated in osteosarcoma tissues and drug-resistant cells.
  • miR-340 directly targets ZEB1, negatively regulating its expression.
  • Overexpression of miR-340 reduced multidrug resistance-1 and P-gp expression, enhancing sensitivity to cisplatin (DDP) by inhibiting viability and promoting apoptosis.
  • Ectopic ZEB1 expression reversed the effects of miR-340, confirming its role in mediating chemoresistance.

Conclusions:

  • miR-340 plays a critical role in alleviating chemoresistance in osteosarcoma by targeting ZEB1.
  • Targeting miR-340 represents a promising therapeutic strategy for overcoming drug resistance in osteosarcoma.

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