Search

Background: To explore the anti‐tumor and anti‐virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. Methods: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV‐related hepatocellular carcinoma (HBV‐related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV‐related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin‐dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. Results: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV‐related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV‐related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high‐risk group, while the OS rate was low. The 1‐year, 3‐year and 5‐year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. Conclusions: Quercetin is a key ingredient of anti‐HBV‐related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is a life‐threatening cancer. Long noncoding RNAs participate in HBV‐related HCC progression. Based on the bioinformatics analysis, LINC00924 downregulation is positively related to unfavorable outcomes in patients with HBV‐related HCC. Herein, we detected the biological functions and regulatory system of LINC00924 in HCC. The LINC00924 downregulation in HBV‐related HCC tissues and cells was revealed by reverse transcription‐quantitative polymerase chain reaction. Functionally, as Transwell assays and western blotting indicated, LINC00924 elevation inhibited HCC cell invasion and epithelial‐mesenchymal transition (EMT). The binding site between LINC00924 and miR‐6755‐5p was determined by luciferase reporter assays. miR‐6755‐5p was confirmed to target NDRG2. miR‐6755‐5p upregulation decreased NDRG2 messenger RNA (mRNA) and protein levels. The mRNA and protein levels of NDRG2 were downregulated in tissues and cells. NDRG2 knockdown attenuated the inhibition induced by LINC00924 overexpression on invasion and EMT of HCC cells. In summary, LINC00924 increases NDRG2 expression to inhibit EMT by targeting miR‐6755‐5p in HBV‐related HCC. HIGHLIGHTS: LINC00924 upregulation inhibits the epithelial‐mesenchymal transition of HBV‐related HCC cellsLINC00924 sponges miR‐6755‐5p that targets NDRG2NDRG2 inhibition reverses the inhibitory effects of LINC00924 elevation on cell malignancy [ABSTRACT FROM AUTHOR]

Background: Long non‐coding RNA (lncRNA) plays an essential role in hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) occurrence and development. Single nucleotide polymorphism (SNP) may affect HBV‐related HCC susceptibility by altering the function of lncRNA. However, the relationship between lncRNA SNPs and HBV‐related HCC occurrence and development is still unclear. Methods: In the present study, based on HBV‐related HCC genome‐wide association studies, eight potentially functional SNPs from two lncRNAs were predicted using a set of bioinformatics strategies. In 643 HBV‐related HCC patients, 549 CHB carriers, and 553 HBV natural clearance subjects from Southern Chinese, we evaluated associations between SNPs and HBV‐related HCC occurrence or development with odds ratio (OR) and 95% confidence interval (CI) under credible genetic models. Results: In HBV‐related HCC patients, rs9908998 was found to significantly increase the risk of lymphatic metastasis under recessive model (Adjusted OR = 1.95, 95% CI = 1.20–3.17). Lnc‐RP11‐150O12.3 rs2275959, rs1008547, and rs11776545 with cancer family history may show significant multiplicative and additive interactions on HBV‐related HCC susceptibility (all pAdjusted <.05). The associations of rs2275959, rs1008547, and rs11776545 with distant metastasis of HBV‐related HCC patients were observed in additive model (Adjusted OR = 1.45, 95% CI = 1.06–1.97 for rs2275959; Adjusted OR = 1.45, 95% CI = 1.06–1.98 for rs1008547; Adjusted OR = 1.40, 95% CI = 1.03–1.91 for rs11776545). Conclusion: Taken together, lnc‐ACACA‐1 rs9908998, lnc‐RP11‐150O12.3 rs2275959, rs1008547, and rs11776545 might be predictors for HBV‐related HCC risk or prognosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer mortality in New Zealand due to endemic hepatitis B virus (HBV) infection and recent hepatitis C virus (HCV) and obesity epidemics. Aim: To describe the changing landscape of HCC referred to a national HCC service over a 20‐year period, including trends in underlying liver disease, screening uptake and access to curative treatments, and to determine the impact of screening on outcomes with a comparison between screened detected and non‐screened detected cases. Methods: All newly diagnosed cases of HCC referred to New Zealand Liver Transplant Unit between 1998 and 2017 were included. Data on patient demographics, liver disease aetiology, screening status and treatment modalities were collected. Results: HCC diagnosis rates have increased from 24 cases in 1998 to 250 in 2017, an increase of 20% per annum. The total of 1985 HCC cases was divided into three cohorts (Era 1: 1998–2009; Era 2: 2009–2014; Era 3: 2014–2017), each comprising 661–662 patients. During the study period, overall survival improved (P = 0.005). The proportion with screen‐detected HCC was similar across the three cohorts (44% in Era 1, 42% in Era 2 and 47% in Era 3). Five‐ and 10‐year survival was higher in screen‐detected cases (49 and 43%) than in non‐screen detected cases (14 and 10%), P < 0.0001. Survival was higher in patients with HCV and HBV than in those with non‐alcoholic steatohepatitis (NASH) or alcoholic liver disease (ALD) – 5 and 10‐year survival was 40 and 34% in HCV‐HCC, 30 and 26% in HBV–HCC, 15 and 14% in NASH‐HCC, 13 and 10% in ALD‐HCC, P < 0.0001. Conclusion: Better outcomes in patients with HBV‐ or HCV‐related HCC than in those with NASH‐related or ALD‐related HCV may reflect better screening uptake and better access to curative therapies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Hepatitis B virus (HBV) is one of the leading causes of HCC, but the precise mechanisms by which this infection promotes cancer development are not fully understood. Recently, miR‐340‐5p, a microRNA (miRNA) that has been identified as a cancer suppressor gene, was found to inhibit the migration and invasion of liver cancer cells. However, the effect of miR‐340‐5p on cell proliferation and apoptosis in HBV‐associated HCC remains unknown. In our study, we show that miR‐340‐5p plays an important role during HBV infection and hepatocellular carcinoma development. Specifically, this miRNA directly binds to the mRNA encoding activating transcription factor 7 (ATF7), a protein that both promotes cell proliferation and suppresses apoptosis through its interaction with heat shock protein A member 1B (HSPA1B). We further found that miR‐340‐5p is downregulated by HBV, which enhances ATF7 expression, leading to enhanced cell proliferation and inhibition of apoptosis. Notably, ATF7 is upregulated in HCC tissue, suggesting that HBV may target miR‐340‐5p in vivo to promote ATF7/HSPA1B‐mediated proliferation and apoptosis and regulate liver cancer progression. This work helps to elucidate the complex interactions between HBV and host miRNAs and further suggests that miR‐340‐5p may represent a promising candidate for the development of improved therapeutic strategies for HCC. [ABSTRACT FROM AUTHOR]

Background and Aims The murine double minute 2 ( MDM2) gene encodes a negative regulator of the tumour protein p53. A single nucleotide polymorphism ( SNP) in MDM2 promoter, SNP309 T > G, has been showed to influence MDM2 protein expression and accelerate tumour formation. To investigate further the role of this locus, we examined the association of the SNP with hepatitis B virus ( HBV)-related hepatocellular carcinoma ( HCC) in a northeast Han Chinese population. Methods MDM2 SNP309 was genotyped in 310 HBV-related HCC patients, 314 non- HCC subjects with HBV infection and 480 healthy controls by using a PCR- RFLP method. Results Significant differences of MDM2 SNP309 were detected between HBV-related HCC patients and healthy controls ( OR 1.729, 95% CI 1.369-2.183, P < 0.0001) or non- HCC subjects with HBV infection ( OR 1.351, 95% CI 1.060-1.722, P = 0.015) by a logistic regression analysis. Our data also revealed that subjects with the G allele had higher HBV-related HCC susceptibility than those with the T allele in various genetic models. In a meta-analysis, where we pooled our data with other published studies, the association between this loci and the disease was further confirmed (pooled OR 1.54, 95% CI 1.37-1.72, P < 0.0001). Conclusions These results suggested that the MDM2 SNP309 might influence the risk of developing HBV-related HCC in a northeast Han Chinese population. [ABSTRACT FROM AUTHOR]