The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway
The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway
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长链非编码RNA TDRG1通过miR-93/RhoC通路在上皮性卵巢癌肿瘤发生和进展中的作用
DOI：
10.1002/mc.22749
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发表时间：
2018-02-01
影响因子：
4.6
通讯作者：
Zhao, Yang
中科院分区：
文献类型：
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作者：
Chen, Shuo;Wang, Li-li;Zhao, Yang
作为女性最常诊断的癌症之一，上皮性卵巢癌（EOC）的发生和进展仍然是一个开放的研究领域。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组织中比在正常卵巢组织中高表达，并且表达随着分化而显着不同。 LncRNA TDRG1的下调抑制了EOC细胞的增殖、迁移和侵袭，而其过表达则具有相反的作用。生物信息学预测和双荧光素酶报告基因分析表明，LncRNA TDRG1 可能具有 miRNA-93 (miR-93) 结合位点。 LncRNA TDRG1 下调可上调 miR-93 表达，而其过表达可降低 miR-93 表达。此外，TDRG1下调会降低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，这些蛋白受miR-93调节，而其上调则诱导RhoC、P70S6K、Bcl-xL和MMP2蛋白表达。在体内，LncRNA TDRG1 过表达诱导肿瘤发展和 RhoC 表达。总而言之，我们的结果首次证明 LncRNA TDRG1 可能是 EOC 的一个新的重要诊断和治疗靶点。
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 (P70S6K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6K, 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.