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长链非编码 RNA TDRG1 通过结合和靶向 VEGF-A 蛋白增强子宫内膜癌的致瘤性。

LncRNA TDRG1 enhances tumorigenicity in endometrial carcinoma by binding and targeting VEGF-A protein.

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Key laboratory for Major Obstetric Diseases of Guangdong Province, and Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou 510150, PR China.

Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):3013-3021. doi: 10.1016/j.bbadis.2018.06.013. Epub 2018 Jun 18.

Abstract

Endometrial carcinoma is one of the most frequently diagnosed cancers in females. Long non-coding RNAs (lncRNAs) have been associated with cancer; its role in endometrial carcinoma is an emerging area of research. In this article, lncRNA TDRG1 expression in human endometrial carcinoma tissues and normal endometrial tissues was quantified by qRT-PCR. LncRNA TDRG1 was overexpressed or knocked-down in neither HEC-1B nor Ishikawa endometrial carcinoma cells, respectively, to assess cellular phenotype and expression of related molecules. Our results showed that lncRNA TDRG1 was significantly overexpressed in endometrial carcinoma tissues. Overexpression of lncRNA TDRG1 promoted endometrial carcinoma cell viability, invasion and migratory ability, inhibited apoptosis, and upregulated VEGF-A, PI3K, Bcl-2, MMP2 and survivin; knockdown of lncRNA TDRG1 had the opposite effects. LncRNA TDRG1 overexpression increased tumorigenicity in vivo and was associated with the upregulation of VEGF-A. RNA binding protein immunoprecipitation (RIP) assays confirmed that lncRNA TDRG1 directly binds to VEGF-A protein. Furthermore, knockdown of VEGFA in lncRNA TDRG1-overexpressing endometrial carcinoma cells reversed the effects of lncRNA TDRG1 on cell proliferation, invasion, migration and apoptosis. In conclusion, lncRNA TDRG1 may promote endometrial carcinoma cell proliferation and invasion by positively targeting VEGF-A and modulating relative genes.

摘要

子宫内膜癌是女性最常见的癌症之一。长链非编码 RNA(lncRNA)与癌症有关;其在子宫内膜癌中的作用是一个新兴的研究领域。在本文中,通过 qRT-PCR 定量检测了人子宫内膜癌组织和正常子宫内膜组织中 lncRNA TDRG1 的表达。分别在 HEC-1B 和 Ishikawa 子宫内膜癌细胞中过表达或敲低 lncRNA TDRG1,以评估细胞表型和相关分子的表达。我们的结果表明,lncRNA TDRG1 在子宫内膜癌组织中显著过表达。lncRNA TDRG1 的过表达促进了子宫内膜癌细胞的活力、侵袭和迁移能力,抑制了细胞凋亡,并上调了 VEGF-A、PI3K、Bcl-2、MMP2 和 survivin;lncRNA TDRG1 的敲低则产生相反的效果。lncRNA TDRG1 的过表达增加了体内的肿瘤发生能力,并与 VEGF-A 的上调有关。RNA 结合蛋白免疫沉淀(RIP)试验证实 lncRNA TDRG1 可直接与 VEGF-A 蛋白结合。此外,在 lncRNA TDRG1 过表达的子宫内膜癌细胞中敲低 VEGFA 逆转了 lncRNA TDRG1 对细胞增殖、侵袭、迁移和凋亡的影响。总之,lncRNA TDRG1 可能通过正向靶向 VEGF-A 并调节相关基因来促进子宫内膜癌细胞的增殖和侵袭。

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