DNAJC12 activated by HNF1A enhances aerobic glycolysis and drug resistance in non-small cell lung cancer.

Abstract

BackgroundThe DnaJ heat shock protein family member C12 (DNAJC12) gene has been demonstrated to promote lung cancer cell growth and migration by increasing β‑catenin expression. In this study, we aimed to reveal the role of DNAJC12 in modulating aerobic glycolysis and cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC).MethodsBioinformatics analysis was applied to assess the expression levels of DNAJC12 and hepatocyte nuclear factor 1-alpha (HNF1A) in NSCLC tissues and the correlation between DNAJC12 and HNF1A expression levels. Cell Counting Kit-8 (CCK-8), flow cytometry assay, and in vivo tumor formation were used to evaluate cell growth, apoptosis, and tumorigenesis. Luciferase gene reporter assay was adopted to assess the relationship between HNF1A and DNAJC12.ResultsBoth DNAJC12 and HNF1A were overexpressed in NSCLC tissues and cells, and their expressions showed a positive correlation. The HNF1A gene could bind to the promoter of DNAJC12 and promoted its transcription and translation. Overexpression of both DNAJC12 and HNF1A promoted cell growth, aerobic glycolysis, and inhibited cell apoptosis in NCI-H1975 and NCI-H1650 cells, as well as the cell apoptosis induced by DDP. In addition, cell growth and aerobic glycolysis mediated DNAJC12 were reversed by the silencing of β-catenin, and downregulation of DNAJC12 abolished the above roles of HNF1A.ConclusionsThis study revealed that DNAJC12, activated by the transcription factor HNF1A, could enhance aerobic glycolysis and drug resistance to DDP in NSCLC through regulating β-catenin expression.