Abstract

The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, accounting for approximately 90% of liver cancer [1,2]

  • The results revealed that the expression levels of maternally expressed gene 3 (MEG3) and Sex determining Region Y-related HMG-box 11 (SOX11) were down-regulated but miR9-5p was highly expressed in hepatocellular carcinoma (HCC) tissues compared to the corresponding adjacent normal tissues (Figure 1A)

  • MEG3 served as a sponge for miR-9-5p in HCC cells The correlation between MEG3 and miR-9-5p was further explored in HCC cells

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, accounting for approximately 90% of liver cancer [1,2]. Orthotopic liver transplantation, transarterial chemoembolization, radiofrequency ablation, and systemic chemotherapies are available treatments for HCC patients [4]. The regulation of lncRNA for biological processes has diverse molecular mechanisms such as RNA-RNA, RNA-protein, and RNA-DNA interactions [9]. LncRNA maternally expressed gene 3 (MEG3) has been reported to function as a tumor suppressor in various cancers such as hemangioma [10], osteosarcoma [11], and thyroid carcinoma [12], and it can serve as a ceRNA for miR-9-5p to mediate the progression of esophageal cancer [13] and prostate cancer [14]. LncRNA MEG3 has been demonstrated to be downregulated in HCC [15,16], the roles of the interaction between MEG3 and miR-9-5p in HCC have not been reported

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