Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10-3) and rs4911154 (adjusted OR =1.27; 95% CI=1.14-1.43; P value =3.7×10-5) were significantly associated with increased HCC risk. The expression level of circ-ITCH was significantly lower in HCC tissues, compared with that in adjacent tissues (P value < 0.001). Cox regression analysis indicated that high expression of circ-ITCH was associated with favorable survival of HCC (HR=0.45; 95% CI=0.29-0.68; P value < 0.001). These results indicate that circ-ITCH may have an inhibitory effect on HCC, and could serve as susceptibility and prognostic biomarkers for HCC patients.
Background and purposeAlthough high leptin concentration has been shown to be correlated with established vascular risk factors, epidemiologic studies have reported inconclusive results on the association between leptin and cardiovascular diseases (CVD). Therefore, a meta-analysis was performed to evaluate this issue.MethodsWe searched Pubmed, Embase, and the Cochrane Library from their inception to Jan 2016 for both case-control and cohort studies that assessed leptin concentration and CVD risk. Reports with odds ratio (OR), risk ratio (RR) and corresponding 95% confidence intervals (CI) were considered. The data were extracted by two investigators independently.ResultsA total of 13 epidemiologic studies totaling 4257 CVD patients and 26710 controls were included. A significant inverse association was shown between leptin and coronary heart disease (CHD), with an overall OR of 1.16 (95% CI: 1.02–1.32), but not for stroke (OR = 1.21, 95% CI 0.98–1.48) under sociodemographic adjustment. Further adjustment for additional cardiovascular risk factors resulted in ORs of 1.16 (95% CI 0.97–1.40) for CHD and 1.10 (95% CI 0.89–1.35) for stroke. The findings remained when analyses were restricted to high-quality studies and indicated OR estimates of 1.07 (95% CI 0.96–1.19) for CHD and 0.98 (95% CI 0.76–1.25) for stroke. In a subgroup meta-analysis, a high leptin level was not independently associated with CHD in both females (OR = 1.03, 95% CI 0.86–1.23) and males (OR = 1.09, 95% CI 0.95–1.26) or with stroke in both females (OR = 1.13, 95% CI 0.87–1.47) and males (OR = 0.80, 95% CI 0.59–1.09). There was no significant publication bias as suggested by Egger test outcomes.ConclusionsOur findings indicate that high leptin levels may not be associated with risks of CHD and stroke. Further large, well-designed prospective cohort studies are needed to fully evaluate the role of leptin on the risk of CVD.
The mechanisms underlying severe liver injury after brain-dead (BD) donor liver transplantation (BDDLT) remain unclear. In this study, we aimed to explore the roles of lncRNAs and circRNAs in liver injury after BDDLT. Rat liver injury was detected in the sham, BD, control, and BDDLT groups. We examined the expression profiles of lncRNAs and circRNAs in the livers of the BDDLT and control group using microarray analysis. The main functions of the differentially expressed genes were analyzed by gene ontology (GO) and KEGG pathway enrichment analysis. In addition, we used bioinformatic analyses to construct related expression networks. Liver injury was aggravated in the BD and BDDLT groups. We found various mRNAs, lncRNAs, and circRNAs that were differentially expressed in the BDDLT group compared with those in the control group. Coding-noncoding gene co-expression (CNC) network analysis showed that expression of the lncRNA LOC102553657 was associated with that of the apoptosis-related genes including HMOX1 and ATF3. Furthermore, competing endogenous RNAs (ceRNAs) network analysis revealed that the lncRNA LOC103692832 and rno_circRNA_007609 were ceRNAs of rno-miR-135a-5p targeting Atf3, Per2, and Mras. These results suggest that lncRNAs and circRNAs play important roles in the pathogenesis and development of liver injury during BDDLT.
Background: Induction of biliary epithelial cell apoptosis by toxic bile acids is involved in the development of cholestatic disease, but the underlying molecular mechanism is not clear. The purpose of this study was to investigate the molecular mechanisms involved in Sirt6 protection against the apoptosis of human intrahepatic biliary epithelial cells (HiBEC) induced by the bile acid glycochenodeoxycholate (GCDC). Results: Sirt6 was either overexpressed or knocked down in HiBEC, with or without GCDC pretreatment. The CCK-8 assay was used to assess cell viability and, Hoechst 33258 staining was used to determine apoptotic rate. Mitochondrial DNA (mtDNA) copy number, malondialdehyde (MDA) and reactive oxygen species (ROS) production were detected to evaluate the severity of the mitochondrial dysfunction and oxidative stress. The mRNA and protein levels of PGC-1α, Nrf1, and Nrf2 were analyzed using RT-qPCR and western blot assay. The results showed that Sirt6 opposed GCDC-induced apoptosis in HiBEC via up-regulating PGC-1α expression and stabilizing mtDNA. We used agonists and inhibitors of AMPK to demonstrate that Sirt6 increased PGC-1α expression through the AMPK pathway whereas GCDC had the opposite effect. Finally, western blot, luciferase assay, and co-immunoprecipitation were used to describe a direct interaction and acetylation modification of PGC-1α by Sirt6. Conclusion: Our data illuminated that Sirt6 ameliorated GCDC-induced HiBEC apoptosis by upregulating PGC-1α expression through the AMPK pathway and its deacetylation effect.
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