Abstract
Abstract
Background
Ferroptosis is a newly discovered mode of cell death distinct from apoptosis and necrosis, and its activation contributes to anticancer therapy in a variety of cancers. However, the prognostic value of ferroptosis-related genes in non-small cell lung cancer (NSCLC) remains to be further investigated.
Methods
NSCLC transcriptome mRNA-seq data set and corresponding clinical data set were downloaded from the Cancer Genome Atlas (TCGA). Then, bioinformatics approaches were subsequently employed to identify potential prognostic markers. Finally, the effects of candidate markers on NSCLC cell proliferation, migration, and ferroptosis were assessed by CCK8, colony formation, wound-healing assay, and functional assays related to ferroptosis.
Results
A total of 37 common differentially expressed genes were screened based TCGA database. Six overall survival associated genes (ENPP2, ULK1, CP, LURAP1L, HIC1, AKR1C1) were selected to build survival model, of which hub gene AKR1C1 was with high expression and low ferroptosis level in NSCLC tumor. Further research showed that AKR1C1 was related with many pathways involved in the process of ferroptosis and associated with diverse cancer-infiltrating immune cells. Moreover, the results of in vitro experiments indicated that the expression of AKR1C1 was upregulated in NSCLC cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis.
Conclusions
Our study revealed the potential role of ferroptosis-related gene AKR1C1 in NSCLC, which can be used for prognostic prediction in NSCLC.
Funder
the phd start-up fund of guangdong medical university
administration of traditional chinese medicine of guangdong province
science and technology special project of zhanjiang
basic and applied basic research program of guangdong province
program of department of natural resources of guangdong province
fund of southern marine science and engineering guangdong laboratory
discipline construction project of guangdong medical university
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
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