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

作　　者：Xiaobin Chi Zhijian Chen Jianda Yu Xiaohua Xie Zerun Lin Yongbiao Chen Lizhi Lv 

机构地区：[1]Department of Hepatobiliary Surgery,900TH Hospital of Joint Logistics Support Force,Fuzhou,Fujian,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第11期897-906,共10页临床与转化肝病杂志（英文版）

基　　金：supported by the Fujian Natural Science Foundation Project(General)[Grant number:2021J011265];the Fund for Scientific Research Projects of the Organ Transplantation Section of the Joint Logistics Support Force Key Discipline of Joint Logistics Medicine[Grant number:LQZDQG].

摘　　要：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.

关 键 词：Circular RNA microRNA PROGNOSIS Hepatocellular cancer BIOINFORMATICS Tyrosine kinase inhibitor 

分 类 号：R735.7[医药卫生—肿瘤]