Yufeng Yuan

Radiofrequency ablation of unresectable liver tumors: factors associated with incomplete ablation or local recurrence.

BACKGROUND Radiofrequency ablation (RFA) of liver tumors is associated with a risk of incomplete ablation or local recurrence. METHODS One hundred sixty-eight patients with 311 unresectable liver tumors were included. Effects of different variables on incomplete ablation and local recurrence were analyzed. RESULTS There were 132 hepatocellular carcinomas and 179 liver metastases. Tumor size was 24 (±13) mm. Two hundred twenty-six tumors were treated percutaneously, and 85 through open approach (associated with liver resection in 42 cases). There was no mortality. Major morbidity rate was 7%. Incomplete ablation and local recurrence rates were 14% and 18.6%. Follow-up was 29 months. On multivariate analysis, factors associated with incomplete ablation were tumor size (>30 mm vs ≤30 mm, P = .004) and approach (percutaneous vs open, P = .0001). Factors associated with local recurrence were tumor size (>30 mm vs ≤30 mm, P = .02) and patient age (>65 years vs ≤65 years, P = .05). CONCLUSIONS RFA is effective to treat unresectable liver tumors. However, there is a risk of incomplete ablation when percutaneously treating tumors >30 mm. When tumor ablation is completely achieved, the main factor associated with local recurrence is tumor size >30 mm.

Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy.

Biliary complications in living liver donors

With the increasing use of living donor liver transplantation (LDLT), the morbidity and mortality of the donors have thus become inevitable problems associated with this procedure. The most common postoperative complications among donors for LDLT involve the biliary tract. The incidence of biliary complications in donors tends to be about 5% based on recent publications. Anatomical variations in the biliary tract, higher predonation alkaline phosphatase levels, and intraoperative blood transfusions are also risk factors for biliary complications in the donors after donation. Donors with biliary complications often show unspecific symptoms and most of the biliary complications can be normally treated by nonsurgical methods. Interventional procedures such as percutaneous placement of a peritoneal drain, percutaneous/endoscopic biliary drainage, and combinations of balloon dilatation and/or stenting are effective in the treatment of bile leakage and biliary stricture. A clear understanding of the biliary anatomy of each donor and refined surgical techniques will help to minimize risk of biliary complications for living liver donors.

Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is third leading cause of cancer-related death globally. Evidence suggest that long non-coding RNAs (lncRNAs) have emerged as key regulators of tumorigenesis and metastasis in HCC. In this study, we investigated the functional significance of SNHG12 and explored whether SNHG12 can directly interact with miR-199a/b-5p in the progression of HCC.MethodsWe determined the expression level of SNHG12 in HCC tissues with quantitative real-time PCR and then studied its clinical significance. The binding site between SNHG12 and miR-199a/b-5p was confirmed using dual luciferase assay and RNA immunoprecipitation (RIP) assay. SNHG12 was silenced through the siRNA transfection to determine whether SNHG12-siRNA is able to affect cell proliferation, invasion and metastasis.ResultsSNHG12 was significantly higher in the HCC tissues than that in the adjacent normal tissues. There were direct interactions between miR-199a/b-5p and the binding site of SNHG12. SNHG12 functioned as an endogenous sponge for miR-199a/b-5p to regulate the expression of MLK3 and affect the NF-κB pathway.ConclusionSNHG12 may serve as a valuable biomarker and a potential therapeutic target for HCC.

Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have malfunctioning roles in the development of human cancers. We globally investigated the molecular mechanisms by which snoRNA host gene 6 (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in hepatoma cell lines and is closely associated with histologic grade, hepatitis B virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in patients with HCC. Knockdown of SNHG6 induced apoptosis and repressed cell cycle progression in hepatoma cell lines, whereas transgenic expression of SNHG6 in the immortalized human hepatic cell line L02 had opposite effects. Xenograft tumors grown from SNHG6-knockdown cells had smaller mean volumes than did tumors grown from control cells. SNHG6 may act as a competing endogenous RNA, effectively becoming a sink for miR-101-3p and thereby modulating the derepression of zinc finger E-box binding homeobox 1, imposing an additional level of post-transcriptional regulation. Functionally, SNHG6 promotes tumor growth and metastasis by inducing epithelial to mesenchymal transition. Further investigations showed that SNHG6 could affect HCC tumorigenesis by binding to up-frameshift protein 1 and regulating Smad7 expression.

Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population.

KLF6 inhibits estrogen receptor-mediated cell growth in breast cancer via a c-Src-mediated pathway

Estrogen receptors play a key role in breast cancer development and progression. Kruppel-like factor 6 (KLF6) is a tumour-suppressing protein. The aim of this study was to identify the role of KLF6 inhibition in estrogen receptor{alpha} (ERα)-elicited breast cancer development. Protein expression levels were examined by western blot analysis and immunoprecipitation was used to analyse interactions between proteins. An MTT assay was used to study cell proliferation. We found that KLF6 mediates cell growth in ERα-positive breast cancer cells through interaction with the c-Src protein. This interaction causes inactivation of the Erk and Akt proteins. These pathways are critical for the proliferation and survival of breast cancer cells. We also established that KLF6 could not mediate cell growth in ERα-negative cells. We conclude that KLF6 can modulate ERα-mediated cell growth in breast cancer cells. The unique role of KLF6 in mediating cell growth in breast cancer cells opens up the possibility of a new therapeutic strategy for treating breast cancer.

The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma

BackgroundIn spite of progress in diagnostics and treatment of Hepatocellular Carcinoma (HCC), its prognosis remains poor, and improved treatment strategies for HCC require detailed understanding of the underlying mechanism. In this investigation we studied the role of Up-frameshift 1 (UPF1) in the tumorigenesis of HCC.MethodsWe determined the expression level of UPF1 in HCC tissues with quantitative real-time PCR and western blotting and then studied its clinical significance. Sodium bisulfite sequencing was used to investigate the regulation of UPF1. We explored the biological significance of UPF1 with gain-and-loss-of-function analyses both in vitro and in vivo. The relationship between UPF1 and SMAD7 was also investigated by western blotting and immunofluorescence.ResultsA great downregulation of UPF1 due to promoter hypermethylation was observed in tumor tissues compared to their adjacent normal tissues. Meanwhile, patients with low UPF1 expression have significantly poorer prognosis than those with high expression. Functionally, UPF1 regulated HCC tumorigenesis both in vitro and in vivo. Moreover, the decreased UPF1 level in HCC reduces NMD efficiency and leads to up-regulation of Smad7, then affects the TGF-β pathway.ConclusionOur findings revealed that UPF1 is a potential tumor suppressive gene and may be a potential therapeutic target for HCC.

Long non-coding RNA PVT1 serves as a competing endogenous RNA for miR-186-5p to promote the tumorigenesis and metastasis of hepatocellular carcinoma

Hepatocellular carcinoma is third leading cause of cancer-related death globally. Long non-coding RNA plasmacytoma variant translocation 1 has been reported to be dysregulated and plays a crucial role in various cancers. In this study, we investigated the interactions between plasmacytoma variant translocation 1 and miR-186-5p in the progression of hepatocellular carcinoma and explored the functional significance of plasmacytoma variant translocation 1. It was determined that plasmacytoma variant translocation 1 was significantly higher, while miR-186-5p was statistically lower in the hepatocellular carcinoma tissues than that in the adjacent normal tissues. Using gain-of-function and loss-of-function methods, our results revealed that plasmacytoma variant translocation 1 affected hepatocellular carcinoma cells proliferation, invasion, and migration. It was found that there was direct interaction between miR-186-5p and the binding site of plasmacytoma variant translocation 1 by performing dual-luciferase assay and RNA immunoprecipitation assay. Furthermore, it was identified that plasmacytoma variant translocation 1 regulated the expression of the miR-186-5p target gene, yes-associated protein 1. Taken together, plasmacytoma variant translocation 1 served as an endogenous sponge for miR-186-5p to reduce its inhibiting effect on yes-associated protein 1 and thus promoted the tumorigenesis of hepatocellular carcinoma.

Downregulation of long non-coding RNAs JPX and XIST is associated with the prognosis of hepatocellular carcinoma

BACKGROUND The expression profiles and biological relevance of long non-coding RNA XIST and its activator JPX in hepatocellular carcinoma (HCC) are not well elucidated. We measured JPX and XIST expression levels in HCC, evaluated their clinical significance in HCC progression, and verified their potential as biomarkers for diagnosing HCC. METHODS JPX and XIST expression in 68 HCC tissues and adjacent normal tissues were evaluated by quantitative reverse transcription-PCR (qRT-PCR); their association with pathologic features and overall survival was analyzed. Plasma JPX/XIST levels in 42 patients with HCC and 68 healthy controls were measured by qRT-PCR to determine their potential as biomarkers. RESULTS JPX and XIST levels were significantly decreased in HCC and associated with histological grade and tumor-node-metastasis stage (P<0.05). Low JPX and XIST expression resulted in significantly poor overall survival of HCC. Multivariate Cox regression analysis demonstrated that JPX/XIST expression levels were independent prognostic factors for HCC overall survival rates. Moreover, plasma JPX levels in patients were lower than that in controls; JPX yielded an area under the receiver operating characteristic curve of 0.814 and the combination of JPX and AFP possessed a promoted ability for discrimination between HCC patients and controls (AUC 0.905, 72.2% specificity, 97.1% sensitivity). CONCLUSIONS Downregulated JPX and XIST may serve as novel biomarkers of poor prognosis in HCC.