DLEU1 contributes to ovarian carcinoma tumourigenesis and development by interacting with miR-490-3p and altering CDK1 expression.

Li-Li Wang,Yin-Ling Xiu,Dan-Dan Wu,Xiu-Bo Sang,Zhi-Hong Zong,Shuo Chen,Yao Liu,Xi Chen,Kai-Xuan Sun,Yang Zhao

doi:10.1111/jcmm.13217

Abstract

Recently, a large number of studies have focused on the important role of long non‐coding RNAs (lncRNAs) in metabolism and development and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases. The lncRNA DLEU1 is involved in many solid tumours and haematological malignancies. However, its role in epithelial ovarian carcinoma (EOC) and the associated molecular mechanisms has not been reported. In this study, quantitative reverse transcription–PCR (qRT–PCR) demonstrated higher lncRNA DLEU1 expression in EOC tissues than in normal tissues. Plasmid transfection of DLEU1 to up‐regulate its expression in the ovarian cancer cell lines A2780 and OVCAR3 increased cell proliferation, migration, and invasion, while inhibited apoptosis. Nude mouse xenograft assay demonstrated that DLEU1 overexpression promoted tumour growth in vivo. QRT–PCR showed decreased miR‐490‐3p expression, while Western blotting demonstrated increased its target genes CDK1, cyclinD1 and SMARCD1, as well as matrix metalloproteinase‐2 (MMP2), Bcl‐xL and P70S6K protein expression, respectively. Short interfering RNA silencing of DLEU1 produced opposite results, where qRT–PCR showed increased miR‐490‐3p expression. The dual‐luciferase reporter assay revealed a direct interaction between DLEU1 and miR‐490‐3p. MiR‐490‐3p plays a tumour suppressor role in epithelial ovarian cancer by targeting CDK1 regulation and influencing SMARCD1 and cyclin D1 (CCND1) expressions. Therefore, we suggest that through interaction with miR‐490‐3p, DLEU1 may influence the expression of CDK1, CCND1 and SMARCD1 protein, subsequently promoting the development and progression of EOC.

Highlights

epithelial ovarian carcinoma (EOC) is the most common reason for reproductive system cancerrelated death; most patients are diagnosed at the late stage, and the 5-year survival rate is
DLEU1 expression is associated with EOC tumourigenesis and progression quantitative reverse transcription–PCR (qRT–PCR) showed significantly higher long non-coding RNAs (lncRNAs) DLEU1 expression in EOC tissues than in normal ovarian tissues, benign ovarian tumours and borderline ovarian tumours (Fig. 1A, P < 0.05), and lncRNA DLEU1 expression was positively associated with differentiation, and International Federation of Gynecology and Obstetrics (FIGO) staging
Exploration of the pathogenesis and development mechanisms of cancer is very important, and the role played by lncRNAs therein has attracted widespread attention

Summary

Introduction

EOC is the most common reason for reproductive system cancerrelated death; most patients are diagnosed at the late stage, and the 5-year survival rate is 200 nucleotides in length. As they lack a significant open reading frame, they cannot encode proteins [5, 6]. Studies have shown that lncRNAs have powerful gene regulatory function and are involved in various pathophysiological processes [7, 8], and play an important role in cancer development [9, 10]. We explored the role of DLEU1 in EOC, and the corresponding molecular mechanism

Methods

Results

Conclusion