MicroRNA-1305 Inhibits the Stemness of LCSCs and Tumorigenesis by Repressing the UBE2T-Dependent Akt-Signaling Pathway

Xiaoyong Wei; Xiaolong You; Jianlong Zhang; Cuncai Zhou

doi:10.1016/j.omtn.2019.04.013

MicroRNA-1305 Inhibits the Stemness of LCSCs and Tumorigenesis by Repressing the UBE2T-Dependent Akt-Signaling Pathway

Mol Ther Nucleic Acids. 2019 Jun 7:16:721-732. doi: 10.1016/j.omtn.2019.04.013. Epub 2019 Apr 22.

Authors

Xiaoyong Wei¹, Xiaolong You¹, Jianlong Zhang¹, Cuncai Zhou²

Affiliations

¹ Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, P.R. China.
² Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, P.R. China. Electronic address: zhoucuncai_zcc@yeah.net.

Abstract

MicroRNAs (miRNAs) are involved in the maintenance of the cancer stem cell (CSC) phenotype by binding to genes and proteins that modulate cell proliferation and/or cell apoptosis. In our study, we aimed to investigate the role of miR-1305 in the proliferation and self-renewal of liver CSCs (LCSCs) via the ubiquitin-conjugating enzyme E2T (UBE2T)-mediated Akt-signaling pathway. Differentially expressed genes in human hepatocellular carcinoma (HCC) were obtained by in silico analysis. The relationship between miR-1305 and UBE2T was verified by dual luciferase reporter gene assay. qRT-PCR and western blot analysis were performed to determine the expression of UBE2T, the Akt-signaling pathway, and stemness-related factors in LCSCs. In addition, miR-1305 disrupted the activation of the Akt-signaling pathway by targeting UBE2T, and, ultimately, it repressed the sphere formation, colony formation, and proliferation, as well as tumorigenicity of LCSCs. In summary, miR-1305 targeted UBE2T to inhibit the Akt-signaling pathway, thereby suppressing the self-renewal and tumorigenicity of LCSCs. Those findings may provide an enhanced understanding of miR-1305 as a therapeutic target to limit the progression of LCSCs.

Keywords: Akt-signaling pathway; hepatocellular carcinoma; liver cancer stem cells; microRNA-1305; self-renewal; stemness; tumorigenicity; ubiquitin-conjugating enzyme E2T.