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OPA1 supports mitochondrial dynamics and immune evasion to CD8+ T cell in lung adenocarcinoma

Authors :
Ying Wang
Yadong Li
Xuanwei Jiang
Yayun Gu
Hui Zheng
Xiaoxuan Wang
Haotian Zhang
Jixiang Wu
Yang Cheng
Source :
PeerJ, Vol 10, p e14543 (2022)
Publication Year :
2022
Publisher :
PeerJ Inc., 2022.

Abstract

Background Mitochondrial fusion and fission were identified to play key roles during multiple biology process. Thus, we aim to investigate the roles of OPA1 in mitochondria fusion and immune evasion of non-small cell lung cancer cells. Methods The transcriptional activation of genes related to mitochondrial dynamics was determined by using multi-omics data in lung adenocarcinoma (LUAD). We elucidated the molecular mechanism and roles of OPA1 promoting lung cancer through single-cell sequencing and molecular biological experiments. Results Here, we found that copy number amplification of OPA1 and MFN1 were co-occurring and synergistically activated in tumor epithelial cells in lung cancer tissues. Both of OPA1 and MFN1 were highly expressed in LUAD tumor tissues and OPA1 high expression was associated with poor prognosis. In terms of mechanism, the damaged mitochondria activated the apoptotic signaling pathways, inducing cell cycle arrest and cell apoptosis. More interestingly, OPA1 deficiency damaged mitochondrial dynamics and further blocked the respiratory function to increase the sensitivity of tumor epithelial to CD8+ T cells in non-small cell lung cancer. Conclusions Our study demonstrated the high co-occurrence of copy number amplification and co-expression of OPA1 and MFN1 in LUAD tissue, and further revealed the contribution of OPA1 in maintaining the mitochondria respiratory function and the ability of immune evasion to CD8+ T cells of LUAD.

Details

Language :
English
ISSN :
21678359
Volume :
10
Database :
Directory of Open Access Journals
Journal :
PeerJ
Publication Type :
Academic Journal
Accession number :
edsdoj.233bf8404df34d1e8a1ef2ad2226557e
Document Type :
article
Full Text :
https://doi.org/10.7717/peerj.14543