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MiR-367 negatively regulates apoptosis induced by adriamycin in osteosarcoma cells by targeting KLF4

Guang-Chao Wang1, Qian-Yun He1, Da-Ke Tong1

  • 1Department of Orthopedics, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.

Journal of Bone Oncology
|June 24, 2016
PubMed

Insights

MicroRNA-367 (miR-367) is elevated in osteosarcoma and contributes to adriamycin (ADR) resistance by downregulating KLF4. This suggests miR-367 is a potential biomarker and therapeutic target for osteosarcoma chemotherapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) play diverse roles in osteosarcoma (OS) tumorigenesis, including regulating proliferation, invasion, migration, apoptosis, and drug resistance.
  • MiR-367 is identified as an oncogene and is frequently upregulated in OS.
  • The specific role of miR-367 in mediating drug resistance in OS cells remains largely unexplored.

Purpose of the Study:

  • To investigate the function of miR-367 in adriamycin (ADR) resistance in osteosarcoma (OS) cells.
  • To identify the molecular mechanisms underlying miR-367's role in OS drug resistance.
  • To evaluate the potential of miR-367 as a biomarker and therapeutic target for OS chemotherapy.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to measure miR-367 expression in OS tissues and cell lines.
  • Western blot analysis to assess protein levels of KLF4, Bax, and cleaved caspase-3.
  • Luciferase reporter assay to confirm KLF4 as a direct target of miR-367.
  • Transfection with miR-367 mimics and inhibitors (anti-miR-367) to manipulate miR-367 levels in OS cells.

Main Results:

  • MiR-367 expression was significantly upregulated in OS tissues and cell lines.
  • Adriamycin (ADR) treatment induced apoptosis in OS cells and concurrently upregulated miR-367.
  • KLF4 was confirmed as a direct target of miR-367, with miR-367 negatively regulating KLF4 expression at both mRNA and protein levels.
  • Overexpression of miR-367 suppressed ADR-induced KLF4 upregulation and apoptosis-related proteins (Bax, cleaved caspase-3), effects reversed by anti-miR-367.
  • Conversely, anti-miR-367 transfection reversed the effects of miR-367 overexpression on KLF4 and apoptosis markers.

Conclusions:

  • MiR-367 plays a crucial role in mediating adriamycin (ADR) resistance in osteosarcoma (OS) by targeting KLF4.
  • The miR-367/KLF4 axis influences apoptosis pathways in OS cells.
  • MiR-367 represents a potential biomarker for predicting chemotherapy resistance in OS and a promising therapeutic target for overcoming drug resistance.
Keywords:
AdriamycinApoptosisChemotherapy resistanceKLF4MiR-367Osteosarcoma

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