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

Xiaobin Chi; Zhijian Chen; Jianda Yu; Xiaohua Xie; Zerun Lin; Yongbiao Chen; Lizhi Lv

doi:10.14218/JCTH.2024.00270

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

J Clin Transl Hepatol. 2024 Nov 28;12(11):897-906. doi: 10.14218/JCTH.2024.00270. Epub 2024 Oct 21.

Authors

Xiaobin Chi¹, Zhijian Chen¹, Jianda Yu¹, Xiaohua Xie¹, Zerun Lin¹, Yongbiao Chen¹, Lizhi Lv¹

Affiliation

¹ Department of Hepatobiliary Surgery, 900TH Hospital of Joint Logistics Support Force, Fuzhou, Fujian, China.

Abstract

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-miRNA-mRNA 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.

Keywords: Bioinformatics; Circular RNA; Hepatocellular cancer; Prognosis; Tyrosine kinase inhibitor; microRNA.