Bioinformatic analysis shows the correlation of hsa_circ_0006220-miR-221/222-3p-ESR1/KDR axis with sorafenib resistance of hepatocellular carcinoma.

ABSTRACT

Sorafenib resistance is a major obstacle influencing its therapeutic efficacy in advanced hepatocellular carcinoma (HCC). The knowledge of circular RNAs (circRNAs), a group of novel endogenous non-coding RNAs, in sorafenib resistance of HCC is still inadequate. In this study, a series of bioinformatic analyses and validation were performed. Firstly, a dataset GSE101850 was included for screening out differentially expressed circRNAs between sorafenib resistant and sensitive HCC, after which the structural patterns and binding microRNAs (miRNAs) of these candidate circRNAs were acquired. By combination of the results from expression, prognosis and diagnosis analysis, miR-221-3p and miR-222-3p were selected as the most potential binding miRNAs of hsa_circ_0006220, which was correlated with sorafenib resistance of HCC. Next, the target genes of miR-221-3p and miR-222-3p were predicted. Subsequently, ESR1 was identified as the top one hub gene among all these target genes. By conducting survival analysis and correlation analysis, ESR1 and KDR were considered as the most potential genes associated with sorafenib resistance of HCC. Collectively, we elucidated a potential hsa_circ_0006220-miR-221/222-3p-ESR1/KDR regulatory axis linked to sorafenib resistance of HCC.