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

**Authors:** Rongkai Shen, Meng Chen, Xia Zhu, Jianhua Lin

PMC · DOI: 10.3389/fcell.2026.1647277 · Frontiers in Cell and Developmental Biology · 2026-03-13

## TL;DR

This study shows that miR-495 suppresses osteosarcoma growth and spread by targeting RUNX3 in the PI3K/Akt pathway.

## Contribution

The novel contribution is identifying miR-495 as a tumor suppressor that targets RUNX3 in osteosarcoma via the PI3K/Akt pathway.

## Key findings

- miR-495 is downregulated in osteosarcoma tissues and correlates with better patient survival.
- miR-495 overexpression inhibits tumor cell proliferation, invasion, and migration while promoting apoptosis.
- RUNX3 is confirmed as a direct target of miR-495 in the PI3K/Akt signaling pathway.

## Abstract

This study aimed to identify miR-495 as a potential regulator in osteosarcoma and characterize its role in tumor progression and underlying signaling pathways.

Differentially expressed miRNAs in osteosarcoma were screened from the GSE39058 dataset using bioinformatics analysis. miR-495 expression was validated in tissues/cells using S-MED database and qPCR. Functional assays, including proliferation, invasion, and apoptosis analyses, were performed following transfection with miR-495 mimics or inhibitors. Transcriptome sequencing combined with dual-luciferase assays identified RUNX3 as a direct target, and Western blot analyzed PI3K/Akt pathway activation.

miR-495 was downregulated in osteosarcoma tissues/cells, positively correlating with patient survival. miR-495 overexpression inhibited cell proliferation, invasion, and migration, while promoting apoptosis by suppressing PI3K/Akt pathway (downregulating p-Akt, Bcl-2; upregulating Bax, c-casp3). RUNX3 overexpression rescued these effects, confirming it as a functional target.

miR-495 acts as a tumor suppressor in osteosarcoma by targeting RUNX3 to inhibit PI3K/Akt signaling, suggesting its potential as a prognostic marker and therapeutic target.

## Linked entities

- **Genes:** MIR495 (microRNA 495) [NCBI Gene 574453], RUNX3 (RUNX family transcription factor 3) [NCBI Gene 864], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], Akt (Akt kinase) [NCBI Gene 41957], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581]
- **Diseases:** osteosarcoma (MONDO:0002623)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, MIR495 (microRNA 495) [NCBI Gene 574453] {aka MIRN495, hsa-mir-495, mir-495}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, RUNX3 (RUNX family transcription factor 3) [NCBI Gene 864] {aka AML2, CBFA3, PEBP2aC}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}
- **Diseases:** osteosarcoma (MESH:D012516), tumor (MESH:D009369), metastasis (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13021609/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC13021609/full.md

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Source: https://tomesphere.com/paper/PMC13021609