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长链非编码 RNA TDRG1 通过 miR-93/RhoC 通路在卵巢上皮性癌发生发展中的作用。

The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway.

机构信息

Department of Gynecology, The First Affiliated Hospital of China, Shenyang, China.

Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, China.

出版信息

Mol Carcinog. 2018 Feb;57(2):225-234. doi: 10.1002/mc.22749. Epub 2017 Nov 6.

Abstract

As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development-related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual-luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR-93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6 K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6 K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC.

摘要

作为女性中最常见的诊断癌症之一,上皮性卵巢癌(EOC)的发展和进展仍然是一个研究领域。长非编码 RNA(lncRNA)在 EOC 中的作用是一个新兴的研究领域。我们发现,LncRNA TDRG1(人类睾丸发育相关基因 1)在 EOC 组织中的表达明显高于正常卵巢组织,且其表达与分化程度差异显著。下调 LncRNA TDRG1 抑制 EOC 细胞增殖、迁移和侵袭,而上调其表达则产生相反的效果。生物信息学预测和双荧光素酶报告基因实验表明,LncRNA TDRG1 可能具有 miRNA-93(miR-93)结合位点。下调 LncRNA TDRG1 可上调 miR-93 的表达,而上调其表达则降低 miR-93 的表达。此外,下调 TDRG1 可降低 miR-93 调控的 Ras 同源基因家族成员 C(RhoC)、p70 核糖体 S6 激酶(P70S6K)、Bcl-xL 和基质金属蛋白酶 2(MMP2)蛋白的表达,而上调 TDRG1 则诱导 RhoC、P70S6K、Bcl-xL 和 MMP2 蛋白的表达。在体内,LncRNA TDRG1 的过表达诱导肿瘤的发展和 RhoC 的表达。总之,我们的研究结果首次表明,LncRNA TDRG1 可能是 EOC 诊断和治疗的一个新的重要靶点。

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