INTRODUCTION

The induction of mitochondrial permeability transition-driven necrosis (MPTDN) is therapeutically relevant in various cancers. However, few studies have explored the role of MPTDN-related genes (MPTDNRGs) in lung adenocarcinoma (LUAD). Therefore, this study investigated the regulatory mechanisms of MPTDNRGs in LUAD.

METHODS

This study was based on The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), GSE31210, and MPTDNRGs. First, the genes obtained from TCGA-LUAD were intersected through differential expression analysis and weighted gene co-expression network analysis (WGCNA) to obtain the candidate gene. An knockdown cell model was constructed using LUAD cells, and cell-related phenotypic experiments, including proliferation and apoptosis, were performed. The integrity of the mitochondrial structure was observed using electron microscopy, and the mitochondrial membrane potential was detected using a JC-1 probe.

RESULTS

A total of 82 candidate genes were identified by intersecting 3,231 differentially expressed genes with 566 key module genes. Subsequently, three prognostic genes (, , and ) were further screened. and were significantly expressed in the LUAD group, whereas the opposite was true for . studies indicated that knockdown significantly inhibited the proliferation of LUAD cells and induced necrosis in these cells. Electron microscopy found that the mitochondrial structure was disrupted after knockdown. The JC-1 probe indicated that the mitochondrial membrane potential in the -knockdown group was significantly reduced, suggesting impaired mitochondrial function.

DISCUSSION

, , and have been identified as being associated with MPTDN in LUAD cells. knockdown may suppress mitochondrial permeability transition through specific pathways, thereby driving LUAD cell necrosis and providing potential targets for subsequent LUAD treatment.