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

Xiaoyong Wei, Xiaolong You + Show 2 more

Open Access

https://doi.org/10.1016/j.omtn.2019.04.013

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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.

Highlights

As the most common primary malignancy in the liver, hepatocellular carcinoma (HCC) is highly prevalent around the globe
We showed that ubiquitin-conjugating enzyme E2T (UBE2T) was found overexpressed in HCC cell lines and liver cancer stem cell (CSC) (LCSCs), and we further revealed that UBE2T promoted proliferation and sphere and colony formation of LCSCs through the Akt-signaling pathway
UBE2T Was Upregulated in HCC Samples Initially, the GEO database was employed in order to retrieve HCCrelated microarray data

Summary

Introduction

As the most common primary malignancy in the liver, hepatocellular carcinoma (HCC) is highly prevalent around the globe. HCC ranks as the fifth most common cancer in males and ninth in women It is the second leading cause of cancer-related mortality in China.[1,2] In addition, eastern and southeastern Asia regions are known to exhibit a high incidence of HCC in the male population.[3] Contrary to other malignancies, HCC patients have an array of treatment options, including surgical resection, chemotherapy, and transplantation.[4] systemic treatment is employed clinically, the mortality rate of HCC still remains to be high because of recurrence and drug resistance.[5] In general, cancer stem cells (CSCs) are dormant or slowly cycling tumor cells, which are capable of reconstituting tumors.[6] CSCs have been observed in solid tumors with a range of stem cell markers, including CD133. CD133+ HCC cells isolated from HCC cell lines and xenograft tumors possess boosted colony formation, proliferation, and tumorigenicity in vivo.[7]

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