DLEU 1 contributes to ovarian carcinoma tumourigenesis and development by interacting with miR‐490‐3p and altering CDK 1 expression
Author(s) -
Wang LiLi,
Sun KaiXuan,
Wu DanDan,
Xiu YinLing,
Chen Xi,
Chen Shuo,
Zong ZhiHong,
Sang XiuBo,
Liu Yao,
Zhao Yang
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13217
Subject(s) - cyclin dependent kinase , ovarian carcinoma , carcinoma , biology , cancer research , ovarian cancer , gene , cancer , genetics , cell cycle
Recently, a large number of studies have focused on the important role of long non‐coding RNA s (lnc RNA s) in metabolism and development and have found that abnormal lnc RNA expression is associated with the pathogenesis and development of many diseases. The lnc RNA DLEU 1 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 lnc RNA DLEU 1 expression in EOC tissues than in normal tissues. Plasmid transfection of DLEU 1 to up‐regulate its expression in the ovarian cancer cell lines A2780 and OVCAR 3 increased cell proliferation, migration, and invasion, while inhibited apoptosis. Nude mouse xenograft assay demonstrated that DLEU 1 overexpression promoted tumour growth in vivo . QRT – PCR showed decreased miR‐490‐3p expression, while Western blotting demonstrated increased its target genes CDK 1 , cyclinD 1 and SMARCD 1 , as well as matrix metalloproteinase‐2 ( MMP 2), Bcl‐ xL and P70S6K protein expression, respectively. Short interfering RNA silencing of DLEU 1 produced opposite results, where qRT – PCR showed increased miR‐490‐3p expression. The dual‐luciferase reporter assay revealed a direct interaction between DLEU 1 and miR‐490‐3p. MiR‐490‐3p plays a tumour suppressor role in epithelial ovarian cancer by targeting CDK 1 regulation and influencing SMARCD 1 and cyclin D1 ( CCND 1) expressions. Therefore, we suggest that through interaction with miR‐490‐3p, DLEU 1 may influence the expression of CDK 1, CCND 1 and SMARCD 1 protein, subsequently promoting the development and progression of EOC.
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