ACTG1 and TLR3 are biomarkers for alcohol‑associated hepatocellular carcinoma

Abstract

Alcohol consumption is a risk factor for the development of hepatocellular carcinoma (HCC); however, the association between alcohol and HCC remains unknown. The present study aimed to identify key genes related to alcohol-associated HCC to improve the current understanding of the pathology of this disease. Alcohol-associated and non-alcohol-associated HCC samples in the GSE50579 dataset of the Gene Omnibus Database were analyzed to investigate altered gene expression. Integrated bioinformatics methods were employed to clarify the biological functions of the differentially expressed genes (DEGs), including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interactions (PPIs). The present study reported that candidate biomarker micro (mi)RNAs via TargetScan Human 7.1. DEGs and their associated miRNAs (according to bioinformatics analysis) were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 284 EGs from the GSE50579 dataset were revealed. In GO term analysis, DEGs were closely associated with the ‘regulation of nucleic acid metabolism’. KEGG pathway analysis indicated that the DEGs were tightly engaged in the ‘VEGF and VEGF receptor signaling network’, ‘proteoglycan syndecan-mediated signaling events’, ‘erbB receptor signaling’ and ‘β1 integrin cell surface interactions’. According to the results of PPI and heat map analysis, the main hub genes were centrin 3 (CETN3), Toll-like receptor 3 (TLR3), receptor tyrosine-protein kinase (ERBB4), heat shock protein family member 8, actin γ1 (ACTG1) and α-smooth muscle actin. it was demonstrated that the ACTG1, TLR3, miR-6819-3p and miRΝΑ (miR)-6877-3P had undefined associations. Furthermore, RT-qPCR analysis revealed that miR-6819-3p and miR-6877-3P may enhance the expression levels of ACTG1 and inhibit the expression levels of TLR3 in alcohol-associated HCC tissues. TLR3 and ACTG1 were proposed as potential biomarkers of alcohol-associated HCC. Investigation into the regulatory functions of miR-6819-3p and miR-6877-3P may provide novel insights into the treatment of alcohol-associated HCC.

TPX2 silencing exerts anti‑tumor effects on hepatocellular carcinoma by regulating the PI3K/AKT signaling pathway

“…In the majority of the patients who undergo radical hepatectomy or liver transplantation, the tumor may exhibit recurrence or may have metastasized (30,31). Although several biomarkers have been thought to be associated with the occurrence and development of liver cancer (32,33), the majority of these markers have not proven beneficial for diagnosing or treating patients with liver cancer. Recently, several novel molecular inhibitors were approved for the treatment of advanced liver cancer, but the overall survival rate of patients has not improved significantly, and the efficacy of these drugs are not promising (34,35).…”

Chronic Alcohol Exposure of Cells Using Controlled Alcohol-Releasing Capillaries

“…A direct exposure to ethanol did not significantly increase the AST levels ( Figure 4 A). Since direct ethanol exposure and ethanol capillary systems show different cellular physiologies, we examined the expression of several genes that were identified as key biomarkers for alcohol-related hepatocellular carcinoma [ 38 , 39 ]. Actin gamma 1 ( ACTG1 ) mRNA levels were significantly increased by treatment with ethanol capillaries for 120 h; however, a direct exposure to ethanol did not change ACTG1 mRNA levels ( Figure 4 C, left).…”

“…In particular, it was previously reported that an increase in ACTG1 expression and a decrease in TLR3 expression could be used as biomarkers for the prognosis of liver cancer due to ethanol [ 38 ]. This previous report was based on the results of a study conducted on 14 patients with hepatocellular carcinoma whose underlying etiology was alcohol (GSE50579) [ 47 ].…”

Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma (Review)

“…Syndecan-1 binds to both the ECM and FGF family. Overexpression of the MMP-9/syndecan-1/FGF-2 axis potentiates the apoptosis pathway in several tumor models (41,42). A previous study demonstrated the role of inhibiting syndecan-1 by synstatin, which exhibits promising antitumor activity against rats with HCC (43).…”

“…Syndecan-1 binds to both the ECM and FGF family. Overexpression of the MMP-9/syndecan-1/FGF-2 axis potentiates the apoptosis pathway in several tumor models ( 41 , 42 ).…”