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

Jingshan Huang^1,2Jia-mei Wang^2,3Ye Yuan^2,4Ting Zhang²Bai-Qiang Li²Fu-Ying Zhao²Liang Hao²Zhan-Wu Yu⁴Hua-Qin Wang^2*

• ¹Shengjing Hospital of China Medical University, Shenyang, China
• ²China Medical University, Shenyang, China
• ³The First Hospital of China Medical University, Shenyang, China
• ⁴Liaoning Cancer Hospital and Institute, Shenyang, China

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 anthanogene (BAG) family is a family of co-chaperones involved in a variety of cellular processes, such as stress signaling, cell cycle and tumorigenesis. BAG5 is the only member of the BAG family that has multiple BAG domains, and its function in non-small cell lung cancer (NSCLC) is largely unknown.Here, we employed a multi-omics approach integrating single cell transcriptomics, proteomics, interactomics, and phosphorproteomics data to obtain a more comprehensive picture of BAG5 function in NSCLC. Based on the multi-omics data and functional analysis using cell lines and patient derived organoid (PDO), the current study demonstrated that BAG5 was involved in regulation of RNA metabolism, mitochondrial dynamics and metabolic reprogramming, as well as cytoskeleton and EMT to promote proliferation and invasion of NSCLC, underscoring its potential role in NSCLC. Our findings provide evidence that BAG5 exerts its oncogenic effects via multiple pathways, which can be exploited as a potential therapeutic target for NSCLC.