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长链非编码RNA牛磺酸上调基因1通过负向调控miRNA-145-5p促进胃癌细胞增殖和侵袭。

Long Noncoding RNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation and Invasion in Gastric Cancer via Negatively Modulating miRNA-145-5p.

作者信息

Ren Kewei, Li Zhen, Li Yahua, Zhang Wenzhe, Han Xinwei

出版信息

Oncol Res. 2017 May 24;25(5):789-798. doi: 10.3727/096504016X14783677992682. Epub 2016 Nov 8.

Abstract

Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is involved in the development and carcinogenesis of various tumors, suggesting the diagnostic potential of TUG1 in these cancers. However, the exact role of TUG1 and its underlying mechanism in gastric cancer (GC) remain unknown. In this study, the expression of TUG1 and miR-145-5p in GC cell lines and nonmalignant gastric epithelial cell lines was detected by qRT-PCR. BGC-823 and SGC-7901 cells were transfected with si-TUG1, pcDNA 3.1-TUG1, miR-145-5p mimics, or matched controls. The biological function of TUG1 and miR-145-5p in GC cell proliferation and invasion in vitro and tumor growth in vivo was investigated by MTT assay, Transwell invasion assay, and tumor xenograft experiments. The regulating relationship between TUG1 and miR-145-5 was confirmed by luciferase reporter assay. The results showed that TUG1 was significantly overexpressed and miR-145-5p was dramatically downregulated in GC cell lines. TUG1 knockdown strikingly inhibited cell proliferation and invasion in vitro and markedly suppressed tumor growth in vivo. Furthermore, TUG1 could directly bind to miR-145-5p and repress miR-145-5p expression. TUG1 overexpression significantly relieved the inhibition on GC cell proliferation and invasion in vitro and tumor growth in vivo, mediated by miR-145-5p overexpression. In conclusion, TUG1 promotes cell proliferation and invasion in GC via negatively modulating miRNA-145-5p, which undoubtedly contributes to understanding the mechanism of GC occurrence and development.

摘要

长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)参与多种肿瘤的发生发展及致癌过程,提示TUG1在这些癌症中具有诊断潜力。然而,TUG1在胃癌(GC)中的确切作用及其潜在机制仍不清楚。在本研究中,通过qRT-PCR检测了TUG1和miR-145-5p在GC细胞系和非恶性胃上皮细胞系中的表达。用si-TUG1、pcDNA 3.1-TUG1、miR-145-5p模拟物或相应对照转染BGC-823和SGC-7901细胞。通过MTT法、Transwell侵袭实验和肿瘤异种移植实验研究了TUG1和miR-145-5p在体外GC细胞增殖和侵袭以及体内肿瘤生长中的生物学功能。通过荧光素酶报告基因实验证实了TUG1与miR-145-5之间的调控关系。结果显示,TUG1在GC细胞系中显著过表达,而miR-145-5p显著下调。敲低TUG1可显著抑制体外细胞增殖和侵袭,并明显抑制体内肿瘤生长。此外,TUG1可直接与miR-145-5p结合并抑制miR-145-5p表达。TUG1过表达显著缓解了miR-145-5p过表达介导的对体外GC细胞增殖和侵袭以及体内肿瘤生长的抑制作用。总之,TUG1通过负向调节miRNA-145-5p促进GC细胞增殖和侵袭,这无疑有助于理解GC发生发展的机制。

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