DNA methylation-regulated HK1 overexpression contributes to irradiation-resistance by promoting glycolysis in non-small cell lung cancer.

Abstract

Irradiation-resistance presents a substantial challenge in the successful application of radiotherapy for non-small-cell lung cancer (NSCLC). However, the specific molecular mechanisms responsible for irradiation-resistance have yet to be completely understood. In this research, the DNA methylation and gene expression patterns resulting from irradiation treatment were produced using the DNA methylation BeadChip and RNA-Seq. An integrated analysis was carried out to identify the genes that are differentially expressed and regulated by DNA methylation. As results, the upregulation of gene expression and downregulation of DNA methylation of hexokinase 1 (HK1), a protein associated with glycolysis, were observed in irradiation-resistant NSCLC cells. Additionally, treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC) resulted in increased expression of HK1. Furthermore, it was found that overexpression of HK1 could enhance irradiation-resistance by impacting glycolysis. Collectively, our study indicate that irradiation-induced alterations in DNA methylation lead to the upregulation of HK1, which in turn promotes glycolysis and contributes to radiotherapy resistance in NSCLC. Therefore, targeting HK1 presents a potential novel strategy for addressing the issue of radiotherapy failure in NSCLC.