# Mechanistic insights into promotion of non-small cell lung cancer by BAG5 using integrative multi-omics approaches

**Authors:** Jing-Shan Huang, Jia-Mei Wang, Ye Yuan, Ting Zhang, Bai-Qiang Li, Fu-Ying Zhao, Liang Hao, Zhan-Wu Yu, Hua-Qin Wang

PMC · DOI: 10.3389/fimmu.2025.1648139 · Frontiers in Immunology · 2025-07-25

## TL;DR

This study explores how BAG5 contributes to non-small cell lung cancer using multi-omics data, revealing its role in cancer cell growth and spread.

## Contribution

The novel contribution is the integrative multi-omics analysis revealing BAG5's role in RNA metabolism, mitochondrial dynamics, and EMT in NSCLC.

## Key findings

- BAG5 regulates RNA metabolism, mitochondrial dynamics, and metabolic reprogramming in NSCLC.
- BAG5 contributes to cytoskeletal remodeling and epithelial-to-mesenchymal transition, promoting cancer cell proliferation and invasion.
- Targeting BAG5 may offer a promising therapeutic strategy for NSCLC treatment.

## Abstract

With the continuous emergence of new technologies in omics, the integrative analysis of multi-omics data has become a new direction to explore life mechanisms. The Bcl-2 associated athanogene (BAG) family consists of co-chaperones involved in various cellular processes, including stress signaling, cell cycle regulation, and tumorigenesis. BAG5, a unique member of this family, contains multiple BAG domains, yet its role in non-small cell lung cancer (NSCLC) remains largely unexplored.

In this study, we employed a multi-omics approach, integrating single-cell transcriptomics, proteomics, interactomics, and phosphoproteomics data to comprehensively investigate BAG5 function in NSCLC. Functional analyses were performed using cell lines and patient-derived organoids (PDOs) to validate our findings.

Our results demonstrate that BAG5 plays a critical role in the regulation of RNA metabolism, mitochondrial dynamics, and metabolic reprogramming. Additionally, BAG5 is involved in cytoskeletal remodeling and epithelial-to-mesenchymal transition (EMT), contributing to the proliferation and invasion of NSCLC cells.

These findings underscore the potential oncogenic role of BAG5 in NSCLC, revealing that it acts through multiple molecular pathways. Our study suggests that targeting BAG5 could be a promising therapeutic strategy for treating NSCLC.

## Linked entities

- **Genes:** BAG5 (BAG cochaperone 5) [NCBI Gene 9529]
- **Diseases:** non-small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** BAG1 (BAG cochaperone 1) [NCBI Gene 573] {aka BAG-1, HAP, RAP46}, BAG5 (BAG cochaperone 5) [NCBI Gene 9529] {aka BAG-5, CMD2F}
- **Diseases:** NSCLC (MESH:D002289), tumorigenesis (MESH:D063646)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12331601/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12331601/full.md

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Source: https://tomesphere.com/paper/PMC12331601