# The role of MiRNA-mediated tumor microenvironment in bone metastasis from a multi-omics perspective: cross-cancer mechanisms and clinical translation

**Authors:** Zhuo Gu, Shu-fen Zhu, Peng-fei Li

PMC · DOI: 10.3389/fonc.2026.1775016 · Frontiers in Oncology · 2026-02-26

## TL;DR

This review explores how miRNAs influence the tumor microenvironment in bone metastasis across prostate, breast, and lung cancers, and how multi-omics and AI can improve diagnosis and treatment.

## Contribution

The paper introduces a cross-cancer multi-omics perspective on miRNA-mediated mechanisms in bone metastasis and their clinical translation potential.

## Key findings

- miRNAs mediate intercellular communication in the tumor microenvironment to regulate immune evasion and bone metabolism.
- miRNA-based liquid biopsies like miR-141-3p and miR-34a show promise for diagnosing and prognosticating bone metastasis.
- Integrating multi-omics data with AI models could enhance miRNA research for precision medicine in cancer treatment.

## Abstract

Bone metastasis is a highly prevalent complication in patients with advanced prostate, breast, and lung cancers, which significantly affects the patient’s prognosis. In recent years, the integration of multi-omics technologies has provided unprecedented insights into the systematic analysis of the highly heterogeneous tumor microenvironment at a systemic level. This review begins with a cross-cancer comparison, systematically outlining the functional similarities and differences in key microenvironment components (e.g., tumor-associated macrophages, cancer-associated fibroblasts, osteoclasts, and T cells) in bone metastasis across these three cancer types. It emphasizes how miRNAs mediate intercellular communication via exosomes to coordinately regulate immune evasion, stromal activation, and bone metabolic reprogramming. We further explored the translational potential of miRNA-based liquid biopsies (e.g., miR-141-3p and miR-34a) for diagnosing and prognosticating bone metastasis in breast, prostate, and lung cancers. Finally, this article looks ahead at how integrating multi-omics data with AI predictive models can overcome current delivery and safety challenges, advancing miRNA research towards the ultimate goal of precision medicine.

## Linked entities

- **Diseases:** prostate cancer (MONDO:0005159), breast cancer (MONDO:0004989), lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}
- **Diseases:** cancer (MESH:D009369), breast, prostate, and lung cancers (MESH:D001943), Bone metastasis (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12979171/full.md

## References

160 references — full list in the complete paper: https://tomesphere.com/paper/PMC12979171/full.md

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Source: https://tomesphere.com/paper/PMC12979171