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EBV miR-BART10-3p 通过靶向 DKK1 促进细胞增殖和迁移。

EBV miR-BART10-3p Promotes Cell Proliferation and Migration by Targeting DKK1.

机构信息

Department of Biomedicine & Health Sciences, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Int J Biol Sci. 2019 Jan 24;15(3):657-667. doi: 10.7150/ijbs.30099. eCollection 2019.

Abstract

In Epstein-Barr virus (EBV)-infected epithelial cancers, HI A rightward transcript (BART) miRNAs are highly expressed. However, only a few target genes of BART miRNAs have been investigated. Our mRNA microarray data showed that DKK1 was markedly down-regulated in EBV-associated gastric carcinoma (EBVaGC) cells. Using luciferase reporter assay we tested whether miR-BART10-3p regulates DKK1 by directly targeting the 3'-UTR of DKK1 mRNA. We observed that miR-BART10-3p transfection decreased DKK1 expression, while an LNA inhibitor of miR-BART10-3p (LNA-miR-BART10-3p(i)) increased DKK1 expression. Furthermore, miR-BART10-3p and siDKK1 promoted cell proliferation and migration. In contrast, transfecting GC cells with LNA-miR-BART10-3p(i) or DKK1 over expression vector suppressed cell proliferation and migration. Our results suggest that miR-BART10-3p may be involved in the tumor progression of EBVaGC by targeting DKK1.

摘要

在 Epstein-Barr 病毒(EBV)感染的上皮性癌中,HI A 右向转录(BART)miRNAs 高度表达。然而,仅研究了 BART miRNAs 的少数几个靶基因。我们的 mRNA 微阵列数据显示,EBV 相关胃癌(EBVaGC)细胞中 DKK1 明显下调。我们通过荧光素酶报告基因检测来测试 miR-BART10-3p 是否通过直接靶向 DKK1 mRNA 的 3'-UTR 来调节 DKK1。我们观察到 miR-BART10-3p 转染降低了 DKK1 的表达,而 miR-BART10-3p 的 LNA 抑制剂(LNA-miR-BART10-3p(i))则增加了 DKK1 的表达。此外,miR-BART10-3p 和 siDKK1 促进了细胞增殖和迁移。相反,用 LNA-miR-BART10-3p(i)或 DKK1 过表达载体转染 GC 细胞可抑制细胞增殖和迁移。我们的研究结果表明,miR-BART10-3p 可能通过靶向 DKK1 参与 EBVaGC 的肿瘤进展。

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