Background: Lung adenocarcinoma (LUAD) exhibits high fatality rates, and effective treatments are lacking. The expression of the N6-methyladenosine (m6A) regulatory protein ALKBH5 is associated with lung cancer. To identify new therapeutic targets for LUAD, we screened target genes of ALKBH5 and analyzed their potential mechanisms of action.
Methods: LUAD samples from The Cancer Genome Atlas (TCGA) were used to analyze the expression of ALKBH5 and screen for genes with correlated expression. Intersection of the genes upregulated in cells with ALKBH5 silencing with the genes significantly associated with ALKBH5 were defined as ALKBH5 target genes. STRING was used to evaluate interactions between the target genes, and the relationship between ALKBH5 target gene expression and LUAD patient prognosis was analyzed using the R package Survminer. Target genes were evaluated by functional enrichment analyses.
Results: ALKBH5 was highly expressed in LUAD tissues and was significantly associated with a poor prognosis. Fifteen ALKBH5 target genes were identified, primarily enriched in protein processing in the endoplasmic reticulum, transcriptional coregulator activity, and cell activation involved in the immune response. Upregulation of ZNF777, TCOF1, CPLX2, and ABL1 was associated with a poor prognosis, whereas upregulation of ZER1, VPS53, and RRBP1 was associated with a good prognosis.
Conclusions: This study provides potential therapeutic targets for LUAD and a basis for further studies on the mechanism underlying the effects of ALKBH5.
Keywords: ALKBH5; Lung adenocarcinoma (LUAD); N6-methyladenosine (m6A); enrichment analysis; prognosis.
2023 Journal of Thoracic Disease. All rights reserved.