Carcinoma, Hepatocellular ; genetics ; Gene Expression ; Humans ; Liver Neoplasms ; genetics

Epigenetic changes refer to stable alterations in gene expression with no underlying modifications in the genetic sequence itself. It has become clear that not only gene variations but also epigenetic modifications may contribute to varied diseases, including cancer. This review will provide an overview of how epigenetic factors, including genomic DNA methylation, histone modifications, and miRNA regulation, contribute to hepatocellular carcinoma (HCC) dissemination, invasion, and metastasis. Additionally, the reversal of dysregulated epigenetic changes has emerged as a potential strategy for the treatment of HCC, and we will summarize the latest epigenetic therapies for HCC.
Carcinoma, Hepatocellular ; genetics ; DNA Methylation ; genetics ; Epigenesis, Genetic ; genetics ; Humans ; Liver Neoplasms ; genetics ; MicroRNAs ; genetics

Carcinoma, Hepatocellular ; genetics ; Cloning, Molecular ; DNA, Complementary ; genetics ; Genes, Neoplasm ; genetics ; Humans ; Liver Neoplasms ; genetics

Autophagy is a programmed cell degradation process that is involved in a variety of physiological and pathological processes including malignant tumors. Abnormal induction of autophagy plays a key role in the development of hepatocellular carcinoma (HCC). We established a prognosis prediction model for hepatocellular carcinoma based on autophagy related genes. Two hundred and four differentially expressed autophagy related genes and basic information and clinical characteristics of 377 registered hepatocellular carcinoma patients were retrieved from the cancer genome atlas database. Cox risk regression analysis was used to identify autophagy-related genes associated with survival, and a prognostic model was constructed based on this. A total of 64 differentially expressed autophagy related genes were identified in hepatocellular carcinoma patients. Five risk factors related to the prognosis of hepatocellular carcinoma patients were determined by univariate and multivariate Cox regression analysis, including TMEM74, BIRC5, SQSTM1, CAPN10 and HSPB8. Age, gender, tumor grade and stage, and risk score were included as variables in multivariate Cox regression analysis. The results showed that risk score was an independent prognostic risk factor for patients with hepatocellular carcinoma ( HR = 1.475, 95% CI = 1.280-1.699, P < 0.001). In addition, the area under the curve of the prognostic risk model was 0.739, indicating that the model had a high accuracy in predicting the prognosis of hepatocellular carcinoma. The results suggest that the new prognostic risk model for hepatocellular carcinoma, established by combining the molecular characteristics and clinical parameters of patients, can effectively predict the prognosis of patients.
Autophagy/genetics* ; Biomarkers, Tumor/genetics* ; Carcinoma, Hepatocellular/pathology* ; Humans ; Liver Neoplasms/pathology* ; Membrane Proteins/genetics* ; Prognosis

Carcinoma, Hepatocellular ; genetics ; DNA, Mitochondrial ; genetics ; Humans ; Liver Neoplasms ; genetics ; Microsatellite Repeats

HCAP1 is a novel hepatic cancer related gene located on human chromosome 17p13.3. The loss of heterozygosity occurred at 17p13.3 in various human cancers. In order to investigate the effects of exogenous HCAP1 gene products on cell proliferation of T lymphoma Jurkat cell line, HCAP1 gene! was transfected into Jurkat cells mediated by liposome, and the cells stably expressing exogenous HCAP1 were screened with G418. The effects of HCAP1 products on cell proliferation were assessed by viable cell count, cell growth curve and colony formation assay in soft agar. The results showed that the HCAP1 transgenic Jurkat cells displayed slow growth rate, extended doubling time and reduced colony formation capability, as compared with the cells transfected with pBK/CMV empty vector (P < 0.01). It is concluded that exogenous HCAP1 gene products could inhibit the proliferation of Jurkat cells.
Carcinoma, Hepatocellular ; genetics ; Cell Division ; Humans ; Jurkat Cells ; Liver Neoplasms ; genetics ; Neoplasm Proteins ; genetics ; Peptides ; Transfection

OBJECTIVETo investigate the expression of microRNA-107 (miR-107) and its functional role in hepatocellular carcinoma(HCC).

METHODSThe gene chip data of HCC obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database were used to analyze the expression levels of miR-107 in liver cancer. Twenty-two pairs of fresh surgical specimens of HCC and adjacent tissues and 53 paraffin-embedded specimens of HCC were examined for miR-107 expression by qRT-PCR. The correlation of the expression levels of miR-107 with the clinicopathologic characteristics of the patients were analyzed. The role of miR-107 in regulating the proliferation of hepatocellular carcinoma cells were determined by MTT assay in Huh7 cells transfected with a miR-107 mimic or inhibitor.

RESULTSThe expression levels of miR-107 were significantly up-regulated in HCC tissues as compared to the adjacent tissues (P<0.05) in positive correlation with the tumor size (P<0.032). Transfection with miR-107 mimics significantly promoted the cell proliferation (P<0.0001) while miR-107 inhibitor inhibited the cell proliferation (P<0.0001).

CONCLUSIONThe expression of miR-107 is up- regulated in HCC tissues and its expression levels are correlated with HCC cell proliferation, suggesting its role as a potential oncogene in liver cancer.

Carcinoma, Hepatocellular ; genetics ; Cell Proliferation ; Humans ; Liver Neoplasms ; genetics ; MicroRNAs ; genetics ; Transcriptional Activation ; Up-Regulation

Carcinoma, Hepatocellular ; genetics ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; genetics

Biomarkers, Tumor ; genetics ; Carcinoma, Hepatocellular ; genetics ; Cell Line ; Hepatocytes ; cytology ; Humans ; Liver Neoplasms ; genetics ; Transfection

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.
Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; Neoplastic Stem Cells ; Prognosis