Inactivation of Acetyl-CoA Acyltransferase 1 enhances the proliferation and motility of nasopharyngeal carcinoma cells

TL;DR

This study shows that lower levels of ACAA1 in nasopharyngeal cancer cells are linked to worse outcomes and suggests ACAA1 could be a new target for treatment.

Contribution

The study identifies ACAA1 as a tumor-suppressor gene and links it to immune evasion in nasopharyngeal carcinoma.

Findings

ACAA1 is downregulated in nasopharyngeal carcinoma and correlates inversely with Epstein-Barr virus gene expression.

Overexpression of ACAA1 inhibits cancer cell proliferation, migration, and invasion.

ACAA1 is associated with immune cell infiltration and immune checkpoint-related genes in the tumor microenvironment.

Abstract

Acetyl-CoA acyltransferase 1 (ACAA1), encoding the peroxisomal 3-ketoacyl-CoA thiolase (POT1), plays a pivotal role in the fatty acid beta-oxidation pathway. Accumulating evidence has linked this enzyme to the onset and development of diverse human malignancies. Here, we observed a marked downregulation of ACAA1 in nasopharyngeal carcinoma (NPC), which displayed an inverse correlation with the expression genes coded by Epstein-Barr virus (EBV). Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis highlighted the potential of ACAA1 as a valuable diagnostic and prognostic biomarker for NPC. Next, gain-of- function experiments were conducted, and the results vividly illustrated that overexpression of ACAA1 potently impeded the proliferation, migration, and invasion of NPC cells. The inhibitory effect was further verified by the reduced Ki−67 staining intensity and the altered distribution pattern of actin filaments, which are crucial indicators of cell proliferation and motility. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant enrichment of immune-related pathways in NPC cells with elevated ACAA1 expression. Moreover, comprehensive xCell, ESTIMATE, and Immunophenoscore analyses underscored the positive association between ACAA1 and immune cell infiltration and the tumor immune effective microenvironment in NPC. Especially, a positive correlation between ACAA1 expression in tumor cells and six immune checkpoint-related genes, namely CD27, PDCD1, CD86, BTLA, TIGIT, and CD28, on immune cells within the tumor microenvironment. Collectively, our findings highlight the potential of ACAA1 as a tumor - suppressor gene and suggest its possible involvement in the immune evasion mechanisms of NPC. This study may provide novel insights into the molecular pathogenesis of NPC and offer new therapeutic targets for this malignancy.

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