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Gastric cancer metastasis associated long noncoding RNA (GMAN), a long noncoding RNA, is associated with metastasis in gastric cancer. However, its underlying mechanisms in hepatocellular carcinoma (HCC) are unclear. We found that lncRNA-GMAN was significantly overexpressed in HCC tissues. GMAN expression is associated with vascular invasion, histological grade, tumor, node, metastasis (TNM) stage, short overall survival, and disease-free survival. Knockdown of GMAN induced apoptosis and suppressed invasive and migration potential in vitro and vivo, whereas ectopic GMAN expression produced the opposite effect. We also found that the inhibition of apoptosis, rather than promotion of proliferation, was responsible for GMAN-enhanced cellular viability. Mechanistic analyses indicated that GMAN directly combined with eukaryotic translation initiation factor 4B (eIF4B) and promoted its phosphorylation at serine-422 by preventing eIF4B binding and dephosphorization of the protein phosphatase 2A subunit B. The results demonstrated the stability of p-eIF4B and the elevation of mRNA translation and anti-apoptosis-related protein expression, which further induced proliferation and metastasis of HCC. The current study demonstrates that GMAN regulates the progression of HCC by inhibiting apoptosis and promoting the survival of cancer cells.

Background Circular RNA (circRNA), an novel type of non-coding RNA, could interact with miRNA and protein molecules to regulate the occurrence and progression of hepatocellular carcinoma (HCC). However, little is known about the pathogenesis of circ_0004913 in HCC. Materials Through the GEO (Gene Expression Omnibus database) to find dysfunctional circRNAs in HCC, and circ_0004913 was selected as the research object. Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression level of circ_0067934 in HCC tissues and cells. CCK-8, Edu and flow cytometry assays were used to determine the malignant behavior of transfected HCC cells. Mechanistically, RNA immunoprecipitation and dual-luciferase reporter gene assay were performed to explore the relation between circ_0067934, miR-1290 and FOXC1 (Forkhead box C1) in HCC. Results The expression of circ_0004913 was down-regulated in HCC tissues and cell lines, while the overexpression of circ_0004913 attenuates the malignant behavior of HCC cells. Bioinformatics predicted that circ_0004913 interacts with miR-1290, which targeted FOXC1 mRNA. In fact, miR-1290 promoted the malignant behavior of HCC cells, while FOXC1 had the opposite effect. In addition, circ_0004913 overexpression enhanced FOXC1 expression by reducing miR-1290 expression, thereby inhibiting the proliferation of HCC cells. Conclusions Circ_0004913 / miR-1290 / FOXC1 regulatory axis could inhibit the progress of HCC. Our findings may provide potential new targets for the diagnosis and treatment of HCC.

Previous studies have shown that long noncoding RNAs (lncRNAs) are capable of regulating cell differentiation and pluripotency. The objective of the present study was to explore the effect of lncRNA cancer upregulated drug resistant (CUDR) on the hepatic differentiation of human umbilical cord mesenchymal stem cells (HuMSCs). HuMSCs were subjected to a hepatogenic differentiation protocol. The level of CUDR was monitored by reverse transcription-quantitative PCR (RT-qPCR) following certain stages of hepatic differentiation. Lentivirus transfection was used to achieve CUDR overexpression. The hepatocyte-related proteins and mRNAs were then examined by immunofluorescence, ELISA and RT-qPCR analyses. The results showed that CUDR was upregulated during the hepatic differentiation of HuMSCs. Upregulation of CUDR can improve hepatic differentiation of HuMSCs, including hepatocyte-related genes and proteins. In addition, it was also found that liver-enriched transcription factors were upregulated after CUDR overexpression. Moreover, there was an association between the Wnt/β-catenin pathway and CUDR. In summary, these results demonstrated that the overexpression of CUDR could improve the hepatic differentiation of HuMSCs, therefore it could be an ideal source for regenerative therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent years, circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of many diseases. A growing number of evidences have identified the representative function of exosomal circRNAs in the physiological state of donor cells, which further induces cellular responses after captured by recipient cells. However, the contributions of circRNAs to HCC remain largely unknown. In vitro and in vivo regulatory roles of circRNA Cdr1as in proliferative and migratory abilities of HCC were evaluated by CCK8, EdU, Transwell and tumourigenicity assays, respectively. Results showed circRNA Cdr1as was highly expressed in HCC cell lines and tissues. Overexpression of circRNA Cdr1as greatly accelerated HCC cells to proliferate and migrate. Mechanistically, we found that Cdr1as could promote the expression of AFP, a well-known biomarker for HCC, by sponging miR-1270. Further studies showed exosomes extracted from HCC cells overexpressing circRNA Cdr1as accelerated the proliferative and migratory abilities of surrounding normal cells. In all, circRNA Cdr1as serves as a ceRNA to promote the progression of HCC. Meanwhile, it is directly transferred from HCC cells to surrounding normal cells via exosomes to further mediate the biological functions of surrounding cells.

The abnormal change of octamer transcription factor 4 (OCT4) is associated with tumor progression; however, its effect on hepatocellular carcinoma (HCC) behavior remains unclear. The purpose of this study was to determine the correlation between HCC and OCT4. In the present study, IHC, western blot analysis, and QRT-PCR were performed to identify differentially expressed OCT4 in a series of HCC tissues and adjacent non-cancerous tissues. In addition, the functions of OCT4 on HCC progression were studied in vitro. Silencing of OCT4 with siRNA was performed in HCC cell lines, and the impact on proliferation, migration, and the EMT marker of HCC was analyzed. Our results found that OCT4 levels were significantly higher in HCC tissues compared with the adjacent non-cancerous tissues. Furthermore, OCT4 siRNA significantly reduced the proliferation rate of SMMC-7721 and HepG2 cells, inhibited the migration and inversion, and could reverse EMT in HCC cells, indicating that OCT4 plays a critical role in HCC progression. Our data suggest that the pathogenesis of human HCC may be mediated by OCT4, and thus, OCT4 could represent selective targets for the molecularly targeted treatments of HCC.

Rationale Angioleiomyoma is an uncommon benign tumor that originates from the vascular smooth muscle cells and contains thick-walled vessels. It can appear anywhere in the body but more frequently in the extremities (especially in the lower limbs) and rarely invades the internal organs. Patient concerns A 52-year-old Chinese woman was referred to our hospital because of finding liver neoplasm 2 weeks ago (case first) and a 64-year-old Chinese woman was admitted to hospital with enlargement of the hepatic neoplasm revealed in follow-up, who was diagnosed with angioleiomyoma of left kidney 2 years ago (case second). Diagnosis All patients were diagnosed with hepatic angioleiomyoma by pathological results. Interventions All patients received surgical treatment, with laparoscopic hepatectomy of the IVb segment in case 1 and laparoscopic hepatic left lateral lobectomy in case 2. Outcomes The 2 patients have eventually recovered, and no recurrences or other complications have been observed so far. Lessons Because of atypical clinical symptoms, no specificity in laboratory examination, and lack of characteristic imaging findings, angioleiomyoma is easily misdiagnosed for another disease of the liver. But with complete resection, the prognosis is generally good.

Aim This meta-analysis aimed to determine whether interferon (IFN) therapy could improve clinical effects of patients with chronic hepatitis B virus (HBV)or hepatitis C virus (HCV) infection-related primary hepatocellular carcinoma (HCC) after surgery. Methods An electronic search from January 1998 to December 2012 was conducted to identify comparative studies evaluating IFN therapy on recurrence and survival after surgical treatment of HCC. Results The estimated odds ratios (OR) for the 1-, 2-, 3- and 5-year overall survival rates of HBV-related HCC were 3.37 (95% confidence interval [CI], 1.18–6.27), 2.36 (95% CI, 1.45–3.83), 1.81 (95% CI, 1.21–2.72) and 1.93 (95% CI, 1.35–2.75), respectively; and the OR for the 1-, 2-, 3- and 5-year recurrence rates were 0.63 (95% CI, 0.44–0.91), 0.84 (95% CI, 0.60–1.18), 0.88 (95% CI, 0.63–1.22) and 0.78 (95% CI, 0.56–1.07), respectively. The overall survival rates of HCV-related HCC were significantly higher in IFN groups than in control groups at 1, 2, 3 and 5 years (OR, 2.10; 95% CI, 0.96–4.55; OR, 1.71; 95% CI, 1.01–2.89; OR, 1.76; 95% CI, 1.09–2.83; and OR, 3.03; 95% CI, 1.97–4.65, respectively); and the recurrence rates of IFN groups were lower than control groups at 1, 2, 3 and 5 years (OR, 0.60; 95% CI, 0.38–0.92; OR, 0.57; 95% CI, 0.41–0.81; OR, 0.58; 95% CI, 0.41–0.80; and OR, 0.52; 95% CI, 0.36–0.75, respectively). Conclusion In conclusion, IFN therapy in this meta-analysis shows a significant clinical effect in postoperative patients of HCC, particularly in HCV-related HCC.

Objective The aim of our study was to retrospectively analyze 15 patients’ clinical materials with laparoscopic resection of liver neoplasms.

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3′UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11–1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68–3.14), and there was a trend for an allele dose effect on risk of HCC (p

Background Recently, a genome-wide association study conducted in Chinese reported a single nucleotide polymorphism at KIF1B , rs17401966, associated with the susceptibility of hepatitis B virus-related hepatocellular carcinoma. In this study, we aim to investigate the effect of rs17401966 on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients at intermediate or advanced stages. Methods The SNP rs17401966 was genotyped using the TaqMan allelic discrimination assay in 414 intermediate or advanced hepatocellular carcinoma patients. Log-rank test and Cox proportional hazard models were used for survival analyses. Results Previous studies have identified that the G allele of rs17401966 demonstrated protective effect for the susceptibility of hepatitis B virus-related hepatocellular carcinoma. Here we found that subjects carrying the G allele of rs17401966 was significantly associated with a better survival compared with those carrying the A allele (adjusted hazard ratio=0.82, 95% confidence intervals=0.68–0.99, P =0.044 in an additive genetic model). Conclusion The variant G allele of rs17401966 may be a favorable biomarker for the prognosis of intermediate or advanced hepatitis B virus-related hepatocellular carcinoma patients in this Chinese population.

Background MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis. Methods We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment. Results The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81–1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59–0.83, P

BACKGROUND: MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients. METHODS: The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis. RESULTS: The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) = 0.76,95% confidence intervals (CI) = 0.59-0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR = 0.72, 95% CI = 0.56-0.91, P = 0.007). CONCLUSIONS: These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.

Background There is no definite agreement on the better therapy (radiofrequency ablation (RFA) versus surgical resection (SR)) for early hepatocellular carcinoma (HCC) eligible for surgical treatments. The purpose of this study is to evaluate the evidence using meta-analytical techniques. Methods A literature search was undertaken until December 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. Results Thirteen articles, comprising two randomized controlled trials(RCTs), were included in the review, with a total of 2,535 patients (1,233 treated with SR and 1,302 with RFA). The overall survival rates were significantly higher in patients treated with SR than RFA after1, 3, and 5 years (respectively: OR, 0.60 (95% CI, 0.42 to 0.86); OR, 0.49 (95% CI, 0.36 to 0.65); OR, 0.60 (95% CI, 0.43 to 0.84)). In the SR group, the 1, 3, and 5 years recurrence rates were significantly lower than the RFA group (respectively: OR, 1.48 (95% CI, 1.05 to 2.08); OR, 1.76 (95% CI, 1.49 to 2.08); OR, 1.68 (95% CI, 1.21 to 2.34)). However, local recurrence between two groups did not exhibit significant difference. For HCC ≤ 3 cm in diameter, SR was better than RFA at the 1, 3, and 5 years overall survival rates (respectively: OR, 0.34 (95% CI, 0.13 to 0.89); OR, 0.56 (95% CI, 0.37 to 0.84); OR, 0.44 (95% CI, 0.31 to 0.62)). This meta-analysis indicated that the complication of SR was higher than RFA (OR, 6.25 (95%CI, 3.12 to 12.52); P = 0.000). Conclusion Although local recurrence between two groups did not exhibit significant difference, SR demonstrated significantly improved survival benefits and lower complications for patients with early HCC, especially for HCC ≤ 3 cm in diameter. These findings should be interpreted carefully, owing to the lower level of evidence.

Certain pseudogenes may regulate their protein-coding cousins by competing for miRNAs and play an active biological role in cancer. However, few studies have focused on the association of genetic variations in pseudogenes with cancer prognosis. We selected six potentially functional single nucleotide polymorphisms (SNPs) in cancer-related pseudogenes, and performed a case-only study to assess the association between those SNPs and the prognosis of hepatocellular carcinoma (HCC) in 331 HBV-positive HCC patients without surgical treatment. Log-rank test and Cox proportional hazard models were used for survival analysis. We found that the A allele of rs9909601 in E2F3P1 was significantly associated with a better prognosis compared with the G allele [adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.56–0.86, P = 0.001]. Additionally, this protective effect was more predominant for patients without chemotherapy and transcatheter hepatic arterial chemoembolization (TACE) treatment. Interestingly, we also detected a statistically significant multiplicative interaction between genotypes of rs9909601 and chemotherapy or TACE status on HCC survival (P for multiplicative interaction < 0.001). These findings indicate that rs9909601 in the pseudogene E2F3P1 may be a genetic marker for HCC prognosis in Chinese.