ACADS acts as a potential methylation biomarker associated with the proliferation and metastasis of hepatocellular carcinomas

Abstract

Background: Hepatocellular carcinomas (HCC) constantly rank among the malignancies with the highest death tolls on the global scale. Moreover, HCC are associated with a limited set of therapeutic options. This is particularly true in the case of advanced stage cancers, where long-term survival is uncommon. For the inoperable, advanced HCC patients, chemotherapy is the main modality of treatment. Due to the lack of known molecular targets, the efficacy of the chemotherapy is limited.Conclusion: These findings clearly indicate that DNA methylation plays a key role in regulating ACADS expression and that it can be a potential therapeutic target for treating HCC.Materials and methods: A thorough comparative analysis of 282 cancer samples with 47 normal samples from GEO datasets resulted in the observation that that the level of ACADS was significantly downregulated in HCC. Loss-of-function analyses were then conducted to understand the biological function of ACADS in HCC. It was noted that ACADS was involved in the proliferation and metastasis of HCC. Experiments involving the knockdown of DMNT expression led to the discovery that the expression of ACADS in the HCC cells was significantly increased. The TCGA database was then employed to identify tumor tissue samples which showed higher methylation levels at cg01535453, cg08618068, and cg10174836 (which are the target sites of the ACADS CpG islands) as compared with normal liver tissue samples. All these findings indicated that ACADS might be a novel methylation biomarker associated with HCC.

Diagnostic Value of the Hypomethylation of the <i>WISP1</i> Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus

“…Cancer develops through the accumulation of genetic and epigenetic aberrations, and epigenetic changes are strongly associated with the development of HCC. As reported, many genes such as ADRAIA, ACADS, UBE2Q1, and ZCCH13 have been found to have aberrant methylation status in HCC (Hu et al 2017;Chen et al 2019;Li et al 2019;Chen et al 2020). Abnormal methylation of genes may be promising biomarkers to timely and accurately distinguish patients with HBV-associated HCC from patients with CHB.…”

Prognostic value of fatty acid metabolism-related genes in patients with hepatocellular carcinoma

“…ACADS is a key short variant of the acyl-CoA dehydrogenase (ACAD) gene family and might be a methylation biomarker in HCC. The expression level of ACADS was negatively correlated with the DNA methylation level [ 25 ]. However, as a key metabolic enzyme, the role of ACADS in fatty acid metabolism in patients with HCC is unclear.…”

Integrated Proteomics and Bioinformatics to Identify Potential Prognostic Biomarkers in Hepatocellular Carcinoma

“…It was reported that DNA methylation plays a key role in regulating ACADS which made it a potential therapeutic target for treating HCC. 37 HSD17B13 is a kind of genetic variants in retinol metabolism, which is associated with liver injury progression. 38 Lu et al found that HSD17B13 was a tumor suppressive gene that inhibits HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio.…”