DLAT, as a Cuproptosis-Related Gene, Regulates Kidney Renal Clear Cell Carcinoma Progression

Abstract

Background: Cuproptosis is a novel discovered cell death mechanism in cancers. This study aimed to investigate the expression and prognostic value of DLAT (dihydrolipidamide s-acetyltransferase), one of the Cuproptosis-related genes, in kidney renal clear cell carcinoma (KIRC) using a comprehensive analysis integrating bioinformatics and experimental assays. Methods: High-throughput data and clinical information of KIRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We used various R packages and bioinformatics analysis websites to analyze DLAT expression and function. Clinical tissue samples were used to verify DLAT expression in KIRC based on real-time quantitative reverse transcription (qRT-PCR) and immunohistochemistry. Subsequently, we validated DLAT differential expression in normal renal cells versus different KIRC cell lines using qRT-PCR. CCK-8 (cell counting kit-8) assay was used to assess the effect of DLAT overexpression on KIRC cells proliferation. Wound healing and Transwell assays were used to assess the effect of DLAT overexpression on KIRC cells invasion and migration. Results: DLAT mRNA expression in KIRC tumor tissue was lower than in normal kidney tissue. DLAT high expression suggested a good prognosis in KIRC. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DLAT was involved in a variety of biological functions and pathways. Infiltration analysis indicated that DLAT might affect the prognosis of KIRC by affecting immune infiltration in the KIRC tumor microenvironment. qRT-PCR and immunohistochemistry further DLAT low expression in KIRC compared to normal kidney tissue. Besides, we found that DLAT overexpression could not only inhibit KIRC cells growth, but also effectively inhibit the migration and invasion of KIRC cell lines. Conclusions: This study explored the expression of DLAT in KIRC and the effect of DLAT on the proliferation, migration, and invasion of renal cancer cell lines, which has a positive role in guiding the diagnosis and treatment of KIRC.