RESUMO
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.
RESUMO
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. 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.