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The aim of our study was to explore the relationship between the methylation status of the alpha-1A adrenergic receptor (ADRA1A) gene and hepatocellular carcinoma (HCC). We combined our in-house data-set with the Cancer Genome Atlas (TCGA) data-set to screen and identify the methylation status and expression of adrenergic receptor (AR) genes in HCC. Immunohistochemistry and western blot were performed to assess the expression of ADRA1A in HCC cell lines and tissues. We further evaluated the methylation levels of the ADRA1A promoter region in 160 HCC patients using the Sequenom MassARRAY® platform and investigated the association between methylation of ADRA1A and clinical characteristics. The expression levels of ADRA1A mRNA and protein were significantly decreased in HCC tissues. Compared with that in paired normal tissues, the mean methylation level of the ADRA1A promoter region was significantly increased in tumour tissues from 160 HCC patients (25.2% vs. 17.0%, P < 0.0001). We found that a DNA methyltransferase inhibitor (decitabine) could increase the expression of ADRA1A mRNA in HCC cell lines. Moreover, hypermethylation of the ADRA1A gene in HCC samples was associated with clinical characteristics, including alcohol intake (P = 0.0097) and alpha-fetoprotein (P = 0.0411). Receiver operator characteristic (ROC) curve analysis demonstrated that the mean methylation levels of ADRA1A could discriminate between HCC tissues and adjacent non-cancerous tissues (AUC = 0.700, P < 0.0001). mRNA sequencing indicated that the main enriched pathways were pathways in cancer, cytokine-cytokine receptor interaction and metabolic pathways (P < 0.01). ADRA1A gene hypermethylation might contribute to HCC initiation and is a promising biomarker for the diagnosis of HCC. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a subtype of a common malignant tumor found in the digestive system. Hsa&#95;circ&#95;0006470 is known to be closely associated with the development of GC. Nevertheless, the mechanism by which hsa&#95;circ&#95;0006470 regulates the tumorigenesis of GC has not been fully elucidated. To investigate the role of hsa&#95;circ&#95;0006470 in GC, its expression levels were assessed in GES-1, AGS, MKN45, and SNU5 cells by reverse transcription-quantitative PCR. Fluorescence in situ hybridization was used to evaluate the localization of hsa&#95;circ&#95;0006470 in AGS and MKN45 cells. In addition, cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to evaluate the viability and proliferation of GC cells, respectively. The dual-luciferase reporter assay was used to explore the interaction among hsa&#95;circ&#95;0006470, microRNA (miR)-1234, and TP53I11. The expression levels of TP53I11, Akt, p-Akt, forkhead box O1, and cyclin dependent kinase 2 in AGS cells were analyzed by Western blotting. The data indicated that hsa&#95;circ&#95;0006470 expression was downregulated in AGS cells. In addition, overexpression (OE) of hsa&#95;circ&#95;0006470 could inhibit the viability and proliferation of GC cells. Moreover, OE of hsa&#95;circ&#95;0006470 inhibited the migration of GC cells and induced G1 cell cycle phase arrest. Moreover, miR-1234 was bound to hsa&#95;circ&#95;0006470 and TP53I11 was targeted by miR-1234. Furthermore, OE of hsa&#95;circ&#95;0006470 inhibited the tumorigenesis of GC via the regulation of the miR-1234/TP53I11 axis. In summary, the present study demonstrated that OE of hsa&#95;circ&#95;0006470 notably inhibited the tumorigenesis of GC by regulating the miR-1234/TP53I11 axis. Therefore, the present study may provide a theoretical basis for exploring novel therapeutic strategies for the treatment of GC.