The Roles And Mechanism Of Exosomal CircRNA Circ-CDYL In Early Stage Of Hepatocellular Carcinoma

Patients with advanced hepatocellular carcinoma(HCC)have a very poor prognosis,so there is an urgent need for early diagnosis of biomarkers for liver cancer.Circ RNA is enriched in exosomes and is extremely stable,so it has great potential to be a diagnostic marker for tumors.In this study,we took BCLC stage 0 HCC(n = 10)as the key research object.The differential expression of Circ RNA in tumor tissues was identified by gene microarray,and the plasma exosomes of 40 early HCC patients and 25 healthy people were subjected to flow cytometry analysis to identify the phenotype of exosomes.This study explored the most significantly upregulated Circ RNA,Circ-CDYL,in hepatocarcinoma tissues,which was confirmed to be enriched in exosomes of HCC patients.For the first time,the exosomes enriched in Circ-CDYL and EPCAM+ liver tumors were defined as ‘Liver-existing exosomes'(LTi-Exos),and it was confirmed that it functions similarly to tumor-initiating cells and promotes the stem cell-like phenotype of HCC.In addition,our results suggested that the combination of LTi-Exos with conventional screening tools using AFP may be helpful for early diagnosis of HCC and the monitoring in high-risk populations in early HCC diagnosis.Subsequently,we further confirmed that Circ-CDYL upregulates the expression of HIF1 AN through ce RNA regulation mechanism,enhances the activity of NOTCH2 pathway,promotes the expression of SURVIVIN,and in turn promotes the development of liver cancer.