miR-141-3p suppresses proliferation and promotes apoptosis by targeting GLI2 in osteosarcoma cells

Nan Wang1, Pengcheng Li1, Wei Liu2

  • 1The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.

Oncology Reports
|December 19, 2017
PubMed

Insights

MicroRNA-141-3p (miR-141-3p) is downregulated in osteosarcoma and inhibits cancer cell proliferation by targeting GLI family zinc finger 2 (GLI2). Restoring miR-141-3p may offer a new therapeutic strategy for osteosarcoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial regulators in various diseases, including osteosarcoma.
  • The specific role of microRNA-141-3p (miR-141-3p) and its target, GLI family zinc finger 2 (GLI2), in osteosarcoma pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the expression levels of miR-141-3p and GLI2 in osteosarcoma.
  • To elucidate the functional relationship between miR-141-3p and GLI2 in osteosarcoma cells.
  • To determine if miR-141-3p exerts its effects through the regulation of GLI2.

Main Methods:

  • Quantitative real-time PCR to measure miRNA and mRNA expression.
  • Western blotting to assess protein levels.
  • Luciferase reporter assays to confirm direct targeting.
  • Cell proliferation and apoptosis assays.
  • Antisense oligonucleotide experiments.

Main Results:

  • Osteosarcoma tissues and cell lines exhibited decreased miR-141-3p expression and increased GLI2 expression.
  • A negative correlation was observed between miR-141-3p and GLI2 levels.
  • Upregulation of miR-141-3p suppressed osteosarcoma cell proliferation and induced apoptosis, accompanied by reduced GLI2 expression.
  • GLI2 was validated as a direct target of miR-141-3p.
  • miR-141-3p negatively regulated GLI2 and its downstream target, parathyroid hormone-related protein 1 (PTHRP1).
  • The anti-proliferative and pro-apoptotic effects of miR-141-3p were mediated via the GLI2 pathway.

Conclusions:

  • miR-141-3p acts as a tumor suppressor in osteosarcoma by targeting GLI2.
  • The miR-141-3p/GLI2 axis plays a significant role in regulating osteosarcoma cell behavior.
  • Targeting the miR-141-3p/GLI2 pathway presents a potential therapeutic avenue for osteosarcoma treatment.

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