Aim: As one of the most common and lethal carcinomas, hepatocellular carcinoma (HCC) is a global health concern and affects millions of people worldwide. Current treatments for HCC are very limited due to its unclear pathogenesis. Here, we aim to further investigate the role of circCMTM3/microRNA (miR)-3619-5p in HCC.Methods: Human blood samples were collected from HCC patients and healthy people. Quantitative reverse transcription-polymerase chain reaction and western blot analysis were undertaken to measure levels of circCMTM3, miR-3619-5p, SOX9, and exosome markers. The MTT, colony formation, and Transwell assays were used to examine the viability, migration, and invasion of human umbilical vein endothelial cells (HUVECs), respectively. Tube formation assay was used to assess angiogenesis. Dual luciferase assay was used to validate circCMTM3/miR-3619-5p and miR-3619-5p/SOX9 interactions. A nude mouse xenograft model was used to test the role of circCMTM3 in HCC in vivo.Results: Levels of circCMTM3 in exosomes from HCC patients and cells were elevated. Knockdown of circCMTM3 greatly decreased viability, migration, and invasion of HUVECs, as well as angiogenesis. CircCMTM3 acted as a miR-3619-5p sponge and miR-3619-5p inhibitor reversed the effects of si-circCMTM3 on angiogenesis. MiR-3619-5p directly targeted SOX9 and modulated angiogenesis through SOX9. Furthermore, knockdown of circCMTM3 suppressed angiogenesis and HCC tumor growth in vivo. Conclusion:The exosome circCMTM3/miR-3619-5p/SOX9 axis from HCC cells promotes angiogenesis and thus contributes to HCC tumorigenesis.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. AIM To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis. METHODS T RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. CONCLUSION This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.

Background: Antineoplastic activity of atractylenolide III (ATL) has been reported in several malignant tumors. However, its activity has not been completely clarified in hepatocellular carcinoma (HCC). Herein, anticancer effects and underlying molecular mechanisms of ATL were investigated in HCC cells in vitro.Methods: Cell viability was evaluated by CCK-8 assay. Cell migration and invasion were evaluated using the transwell assay. TUNEL staining was performed to evaluate cell apoptosis. Protein expression was measured by western blotting analysis. Online database TargetScan and luciferase reporter gene analysis were performed to validate FGFR1 as a target of miR-195-5p.Results: HepG2 and SMMC7721 cell growth, migration, and invasion were inhibited by ATL treatment in a dose-dependent pattern. ATL treatment-induced apoptosis of HepG2 and SMMC7721 cells. Intriguingly, ATL treatment unexpectedly inhibited FGFR1 protein expression in HepG2 and SMMC7721 cells. Knockdown of FGFR1 inhibited proliferation, migration, and invasion, and evoked apoptosis of HepG2 and SMMC7721 cells. We also found that ATL treatment could increase the expression of miR-195-5p, which as a posttranscriptional targeted FGFR1. In HCC tissues, miR-195-5p expression is negatively correlated with FGFR1. Furthermore, the antiproliferative and proapoptotic roles of miR-195-5p were neutralized by overexpressed FGFR1 in HCC cells. Conclusion:ATL effectively repressed growth and induced apoptosis of human HCC cells through the upregulation of miR-195-5p to downregulate FGFR1 expression. Practical applicationsAtractylenolide III as a bioactive anticancer adjuvant medication will provide chemosensitization strategy for reversing the drug resistance of HCC.

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The incidence of hepatocellular carcinoma (HCC) has increased in these years. DNA damage repair (DDR) pathway is required in response to DNA damage Gene mutations in DDR pathway play an important role in different stages of tumorigenesis and development. Based on the importance of DDR pathway in precision therapy of multiple cancers, we analyzed DDR gene mutations in Chinese patients with HCC. The results showed that (tumor mutation burden) TMB was significantly higher in HCC patients who carried somatic mutations in DDR than in non-carriers, and TMB in patients with DS, MMR mutations and DDR genes mutations such as RAD50, MLH1, MSH2, CHEK2 was significantly higher than that in wild-type patients. Based on the results of next-generation sequencing (NGS) testing, we are trying to provide clues for targeted therapy and provide feasible basis for PD-1/PD-L1 immune checkpoint inhibitor therapy.