Three novel circRNAs upregulated in tissue and plasma from hepatocellular carcinoma patients and their regulatory network

Abstract

Background The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored. Methods CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes. Results We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle. Conclusions Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.

RETRACTED ARTICLE: Has_circ_0008583 modulates hepatocellular carcinoma progression through the miR-1301-3p/METTL3 pathway

“…Further experiments proved that circ-0004277 could promote EMT of HCC. Wang et al [ 10 ] identified hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172 were significantly upregulated in HCC tissues, which revealed that circRNAs was a potentially effective target for the treatment of HCC. Recently, Sun et al’s study [ 11 ] showed that hsa_circ_0008583 is highly expressed in HCC tissues, but its role and mechanism in the development of HCC has not been reported.…”

Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

“…According to Wang’s research ( Wang L. et al, 2021 ), miR-18a-3p levels increased in HCC tissues. However, the mechanism of miR-18a-3p in liver cancer still remains elusive.…”

Up-Regulation of VCAN Promotes the Proliferation, Invasion and Migration of HCC and Serves as a Biomarker

“…Previous studies have shown that the expression of hsa-miR-144-3p in hepatocellular carcinoma is signi cantly higher than that in adjacent tissues, and the ratio of HSA144-3p/hsA-miR-21-5p increases signi cantly during the occurrence of hepatocellular carcinoma, which is even better than alpha-fetoprotein in ROC curve analysis, suggesting that HSA144-3p may be an excellent predictive marker of liver cancer (14). In addition, HSA-miR-455-5p has also been proved to be involved in the occurrence and development of liver cancer (15). Further analysis of Starbase showed that the expression of the four miRNAs was negatively correlated with the expression of VCAN in HCC (Figgure 8B).…”