Carcinoma, Hepatocellular ; genetics ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Signal Transduction

Carcinoma, Hepatocellular ; metabolism ; Glypicans ; biosynthesis ; genetics ; Humans ; Liver Neoplasms ; metabolism ; RNA, Messenger ; biosynthesis ; genetics

Carcinoma, Hepatocellular ; metabolism ; pathology ; DNA-Binding Proteins ; genetics ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Phosphoproteins ; genetics ; metabolism ; RNA, Messenger ; genetics

Antigens, CD ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Tetraspanin 24

Carcinoma, Hepatocellular ; metabolism ; Glycoproteins ; biosynthesis ; genetics ; Humans ; Hyaluronan Receptors ; biosynthesis ; genetics ; Liver ; metabolism ; Liver Neoplasms ; metabolism ; Osteopontin ; biosynthesis ; genetics

OBJECTIVE: To detect the expression of RA SAL2 in patients with hepatocellular carcinoma (HCC), and to investigate the association of RASAL2 expression with pathological characteristics and prognosis. METHODS: Immunohistochemical SP method was used to detect the expression of RA SAL2 in 164 samples of HCC tissue and the adjacent tissue. Th e association of RA SAL2 expression with clinical features and prognosis was analyzed. RESULTS: The expression of RASAL2 in adjacent tissue was significantly increased compared to that in HCC tissue (P<0.001). The expression level of RASAL2 was associated with the degree of differentiation, tumor TNM stage and vascular invasion (P<0.001), but not associated with the level of AFP, tumor size, or the number of nodules (P>0.05). The 5 years recurrence-free survival (RFS) in patients with low expression of RASLA2 was significantly reduced compared with that in patients with high expression of RASLA2 (P<0.001). Cox analysis showed that low expression of RASLA2 was the independent factor for recurrence and death in HCC patients after surgery (P<0.001). CONCLUSION Low expression of RRASAL2 is significantly associated with the poor prognosis of HCC, which is an independent factor for HCC prognosis.
Carcinoma, Hepatocellular ; genetics ; metabolism ; Carrier Proteins ; genetics ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Neoplasm Recurrence, Local ; Prognosis

Hepatocellular carcinoma (HCC) is one of the five most common malignant tumors. According to the latest statistics of the World Health Organization (WHO), the incident and mortality rates of HCC ranks the eighth and third in the world, respectively, which severely affect people's health. Exosomes are extracellular vesicles with a bilayer of phospholipids, which carry active substances such as proteins and nucleic acids derived from their mother cells. These exosomes greatly facilitate the exchange of substances and information between cells, and coordinate physiological and pathological processes in the body. In recent years, a large number of studies have shown that exosomal proteins play important roles in the tumorigenesis, development, diagnosis and treatment of HCC. Here we review the composition and functions of exosomes and the role of exosomal proteins in HCC.
Carcinogenesis/genetics* ; Carcinoma, Hepatocellular/therapy* ; Exosomes/metabolism* ; Humans ; Liver Neoplasms/therapy* ; MicroRNAs/genetics* ; Proteomics

OBJECTIVE: To construct the regulatory network of survival-related onco-miRNAs and their target genes in hepatocellular carcinoma (HCC) and verify the interactions between the key miRNAs and their targets. METHODS: We screened survival-related miRNAs in HCC in OncomiR and Oncolnc databases, predicted their target genes using miRNet, and conducted survival and expression analysis using GEPIA2 and Ualcan, respectively. The miRNA-target gene co-expression analysis was performed and the miRNA-target network was constructed. Enrichment analysis was performed in Enrichr and protein-protein interaction analysis in STRING database. We tested the effects of transfection with the mimic or inhibitor of hsa-miR-1226-3p or hsa-miR-221-5p on proliferation of HepG2 cells using CCK8 assay and examined the changes in the expressions of the target genes using RT-qPCR. The effect of transfection with hsa-miR-221-5p mimic or inhibitor on protein expressions of the target genes was examined using Western blotting in. A dual luciferase reporter assay was used to test the interaction between hsa-miR-221-5p and its potential target gene GCDH. We further examined the effect of transfection with hsa-miR-221-5p mimic and pEGFP N1-GCDH, alone or in combination, on proliferation, migration and invasion of HepG2 cells. RESULTS: We identified 223 survival-related miRNAs in HCC from OncomiR and 146 miRNAs from Oncolnc with an intersection of 131 miRNAs, and 48 miRNAs were identified as onco-miRNAs in HCC after survival and expression analysis. Twenty-seven eligible target genes were identified after miRNA-mRNA co-expression analysis. The constructed miRNA-target gene network consisted of 25 miRNAs and 27 target genes. The most enriched term was fatty acid metabolism for the target genes. In HepG2 cells, transfection with the mimic or inhibitor of hsa-miR-1226-3p or hsa-miR-221-5p caused significant changes of the mRNA and protein levels of their respective target genes (P < 0.05). The results of dual luciferase reporter assay confirmed the targeting relationship between hsa-miR-221-5p and GCDH gene (P < 0.05). Transfection with hsa-miR-221-5p mimic significantly suppressed the proliferation, migration and invasion of HepG2 cells, but this effect was obviously relieved by co-transformation with pEGFP N1-GCDH (P < 0.05). CONCLUSION Fatty acid metabolism might be one of the most crucial pathways that mediate the effect of the oncomiRNAs in HCC, and the hsa-miR-221-5p/GCDH axis is an important molecular mechanism for HCC progression.
Carcinoma, Hepatocellular/genetics* ; Gene Regulatory Networks ; Humans ; Liver Neoplasms/pathology* ; MicroRNAs/metabolism* ; RNA, Messenger/metabolism*

Animals ; CD40 Ligand ; genetics ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; therapy ; Genetic Therapy ; Liver Neoplasms ; genetics ; metabolism ; therapy ; Mice ; Neoplasms, Multiple Primary ; genetics ; metabolism ; therapy ; Transgenes ; genetics

Carcinoma, Hepatocellular ; genetics ; metabolism ; DNA Methylation ; DNA Restriction Enzymes ; metabolism ; DNA, Neoplasm ; genetics ; Glutathione S-Transferase pi ; genetics ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods