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miR-495 suppresses osteosarcoma growth and metastasis by directly targeting RUNX3 in the PI3K/Akt pathway in vitro

Rongkai Shen1,2, Meng Chen1,2, Xia Zhu1,2

  • 1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Frontiers in Cell and Developmental Biology
|March 30, 2026
PubMed
Abstract

Insights

MicroRNA-495 (miR-495) functions as a tumor suppressor in osteosarcoma. It inhibits tumor progression by targeting RUNX3 and suppressing the PI3K/Akt pathway, offering potential as a prognostic marker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma is a primary bone malignancy with significant mortality.
  • MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
  • Identifying novel regulatory mechanisms in osteosarcoma is essential for therapeutic advancements.

Purpose of the Study:

  • To investigate the role of miR-495 in osteosarcoma progression.
  • To elucidate the molecular mechanisms underlying miR-495's function.
  • To assess miR-495 as a potential prognostic biomarker and therapeutic target.

Main Methods:

  • Bioinformatic analysis of miRNA expression datasets (GSE39058).
  • Validation of miR-495 expression in osteosarcoma tissues and cell lines.
  • Functional assays (proliferation, invasion, apoptosis) following miR-495 modulation.
  • Identification of direct targets using transcriptome sequencing and dual-luciferase assays.
  • Western blot analysis to assess signaling pathway activation (PI3K/Akt).

Main Results:

  • miR-495 was found to be downregulated in osteosarcoma tissues and cells, correlating with poorer patient survival.
  • Overexpression of miR-495 suppressed osteosarcoma cell proliferation, invasion, and migration while promoting apoptosis.
  • RUNX3 was identified as a direct target of miR-495.
  • miR-495 suppressed the PI3K/Akt signaling pathway, evidenced by changes in p-Akt, Bcl-2, Bax, and c-casp3 levels.
  • RUNX3 overexpression reversed the tumor-suppressive effects of miR-495.

Conclusions:

  • miR-495 acts as a tumor suppressor in osteosarcoma.
  • The tumor-suppressive function of miR-495 is mediated through targeting RUNX3 and inhibiting the PI3K/Akt signaling pathway.
  • miR-495 holds promise as a prognostic biomarker and a potential therapeutic target for osteosarcoma.
Keywords:
PI3K/Akt signaling pathwayRUNX3metastasismiR-495osteosarcoma

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