Role and mechanism of ACOT7 in the malignant progression of head and neck squamous cell carcinoma

WANG Ningbo; FAN Xin; CHEN Wenying; BIAN Ka

doi:10.13276/j.issn.2097-1656.2025.12.010

Abstract：Objective To explore the role and mechanism of acyl-CoA thioesterase 7(ACOT7)in the malignant progression of head and neck squamous cell carcinoma(HNSCC).Methods The expression data of ACOT7 in normal tissues and pan-cancer tissues were downloaded from the TIMER2 database.The expression difference of ACOT7 between the sequencing data of normal tissues and pan-cancer tissues was calculated by differential analysis.The transcriptome sequencing data of HNSCC were downloaded from the TCGA database.The t-test was employed to analyze the expression differences of ACOT7 mRNA levels between HNSCC tissues and normal tissues.The protein expression level of ACOT7 was verified using the HPA database.According to the ACOT7 expression levels and survival data of patients in the TCGA database,the patients were divided into ACOT7 high expression group and ACOT7 low expression group based on the median value of ACOT7.The survminer package was used to analyze and verify the overall survival(OS)and progression-free survival(PFS)of HNSCC patients in the two groups.Meanwhile,the clinical information of HNSCC patients in the TCGA database was utilized to analyze the correlation between ACOT7 expression and the clinical characteristics of HNSCC patients.R package"limma"for differential analysis was used to analyze the differentially expressed genes(DEGs)between the high and low ACOT7 expression groups based on the median value of ACOT7 as the boundary.Functional and signaling pathway enrichment analyses were performed on the DEGs.The corrplot package and the STRING database were used to construct the co-expression and protein-protein interaction(PPI)networks of ACOT7.ACOT7 was knocked down in HSQ89 and CAL27 cells using lentiviruses.Western blotting and qRT-PCR were used to detect the protein expression and mRNA levels of ACOT7.The CCK-8 assay and the plate colony formation assay were used to detect the proliferation ability of cells.Results ACOT7 was highly expressed in various malignant tumor tissues.The mRNA level of ACOT7 in HNSCC tissues was significantly higher than that in normal tissues(P＜0.05,P＜0.01).HNSCC patients with high ACOT7 expression had shorter OS and PFS(P＜0.05,P＜0.01).Patients with high ACOT7 expression had higher T stage and clinical stage(P＜0.05,P＜0.01).At the same time,the ACOT7 level was relatively higher in HPV-negative HNSCC patients(P＜0.05).Moreover,the expression of ACOT7 in the oropharynx was relatively higher than that in the laryngeal tissue(P＜0.05).A total of 1 154 DEGs were obtained from the differential analysis of the two groups grouped by the median expression value of ACOT7,including 176 up-regulated DEGs and 978 down-regulated DEGs(|log2FC|＞1,FDR＜0.05).GO functional enrichment analysis showed that DEGs were significantly enriched in immunoglobulin production,immunoglobulin complex,and antigen binding.KEGG was mainly enriched in the cytoskeleton,neuroactive ligand-receptor interaction,and multiple metabolic pathways.GSEA analysis was mainly enriched in antigen processing and presentation,DNA replication,drug metabolism-cytochrome P450,steroid hormone biosynthesis,taurine and hypotaurine metabolism,and tyrosine metabolism.PPI analysis revealed interactions between ACOT7 and multiple proteins with strong positive(negative)correlations.Compared with the control group,the in vitro proliferation ability and colony-forming ability of HNSCC cells with ACOT7 gene knockdown were weakened(P＜0.01).Conclusion The expression level of ACOT7 is significantly increased in HNSCC.Patients with high ACOT7 expression have a poor prognosis.Down-regulating the expression level of ACOT7 can inhibit the proliferation and colony-forming ability of HNSCC cells in vitro.