Targeting FCRLA to induce necrosis in lung adenocarcinoma: a novel strategy for prognosis and therapy via MPT-Driven
Xiaoli Sun1,2,3,4, Bowen Cai5, Shusen Zhang6
1The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
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 FCRLA gene. An FCRLA knockdown cell model was constructed in vitro 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 (RASGRP2, CD79A, and FCRLA) were further screened. CD79A and FCRLA were significantly expressed in the LUAD group, whereas the opposite was true for RASGRP2. In vitro studies indicated that FCRLA knockdown significantly inhibited the proliferation of LUAD cells and induced necrosis in these cells. Electron microscopy found that the mitochondrial structure was disrupted after FCRLA knockdown. The JC-1 probe indicated that the mitochondrial membrane potential in the FCRLA-knockdown group was significantly reduced, suggesting impaired mitochondrial function.
Discussion:
RASGRP2, CD79A, and FCRLA have been identified as being associated with MPTDN in LUAD cells. FCRLA knockdown may suppress mitochondrial permeability transition through specific pathways, thereby driving LUAD cell necrosis and providing potential targets for subsequent LUAD treatment.
Insights
This study identifies three genes, including FCRLA, linked to mitochondrial permeability transition-driven necrosis in lung adenocarcinoma (LUAD). FCRLA knockdown inhibits LUAD cell proliferation and induces necrosis, suggesting FCRLA as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Mitochondrial permeability transition-driven necrosis (MPTDN) is a relevant therapeutic strategy for various cancers.
- The role of MPTDN-related genes (MPTDNRGs) in lung adenocarcinoma (LUAD) remains underexplored.
Purpose of the Study:
- To investigate the regulatory mechanisms of MPTDNRGs in LUAD.
- To identify novel therapeutic targets for LUAD based on MPTDN pathways.
Main Methods:
- Utilized The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and GSE31210 datasets.
- Employed differential expression analysis and weighted gene co-expression network analysis (WGCNA).
- Constructed an FCRLA knockdown LUAD cell model for in vitro functional assays and mitochondrial assessments.
Main Results:
- Identified 82 candidate genes, subsequently narrowing down to three prognostic genes: RASGRP2, CD79A, and FCRLA.
- FCRLA knockdown significantly inhibited LUAD cell proliferation and induced cell necrosis.
- Observed disrupted mitochondrial structure and reduced mitochondrial membrane potential in FCRLA-knockdown cells.
Conclusions:
- RASGRP2, CD79A, and FCRLA are associated with MPTDN in LUAD.
- FCRLA knockdown suppresses mitochondrial permeability transition, driving LUAD cell necrosis.
- FCRLA represents a potential therapeutic target for LUAD treatment.
