Identification and Validation of the Hsa_circ_0001726/miR-140-3p/KRAS Axis in Hepatocellular Carcinoma Based on Microarray Analyses and Experiments

Background and Aims:Hepatocellular carcinoma(HCC)is one of the most fatal malignancies.Epigenetic mechanisms have revealed that noncoding RNAs,such as microRNAs(miRNAs)and circular RNAs(circRNAs),are involved in HCC progression.This study aimed to construct a circRNA-miRNAmRNA network in HCC and validate one axis within the network.Methods:HCC-related transcriptome data were obtained from the Gene Expression Omnibus,and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs.The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted.The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.Results:We identified six differentially expressed circRNAs in HCC,which were linked to 13 miRNAs and 88 mRNAs.A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed.Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression,possibly through the miR-140-3p/KRAS axis.Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.Conclusions:The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.