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敲低 lncRNA SNHG4 通过靶向 miR-204-5p 抑制胃癌细胞增殖和转移。

Knockdown of lncRNA SNHG4 suppresses gastric cancer cell proliferation and metastasis by targeting miR-204-5p.

机构信息

Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin, China.

出版信息

Neoplasma. 2021 May;68(3):546-556. doi: 10.4149/neo_2021_200914N981. Epub 2021 Feb 11.

Abstract

Long non-coding RNAs (lncRNAs) have been identified as critical regulators in gastric cancer (GC) progression. However, whether lncRNA small nucleolar host gene 4 (SNHG4) functions in GC development remains unknown. In this study, the bio-functional role of SNHG4 and its potential mechanism on GC progression were systematically dissected. To investigate the role of SNHG4 in GC, we silenced SNHG4 using short hairpin RNAs (shRNAs) to perform loss-of-function assays. The results showed that SNHG4 expression in GC cells was at a higher level compared to normal gastric mucosal epithelial cells. Knockdown of SNHG4 dramatically suppressed proliferation, migration and invasion, and blocked cell cycle progression of GC cells. Moreover, knockdown of SNHG4 upregulated microRNA-204-5p (miR-204-5p) expression, whereas downregulated ribonucleotide reductase subunit M2 (RRM2) expression in GC cells. Dual-luciferase reporter assay results showed that miR-204-5p was a direct target of SNHG4. Additionally, knockdown of SNHG4 suppressed GC tumorigenesis in xenograft mouse models. Taken together, these data demonstrated that knockdown of SNHG4 suppressed GC development by targeting miR-204-5p.

摘要

长链非编码 RNA(lncRNA)已被鉴定为胃癌(GC)进展的关键调节因子。然而,lncRNA 小核仁宿主基因 4(SNHG4)是否在 GC 发展中起作用尚不清楚。在这项研究中,系统剖析了 SNHG4 在 GC 进展中的生物功能作用及其潜在机制。为了研究 SNHG4 在 GC 中的作用,我们使用短发夹 RNA(shRNA)沉默 SNHG4 以进行功能丧失测定。结果表明,GC 细胞中的 SNHG4 表达水平高于正常胃黏膜上皮细胞。SNHG4 的敲低显着抑制 GC 细胞的增殖、迁移和侵袭,并阻断细胞周期进程。此外,SNHG4 的敲低上调了 GC 细胞中 microRNA-204-5p(miR-204-5p)的表达,而下调了核糖核苷酸还原酶亚基 M2(RRM2)的表达。双荧光素酶报告基因检测结果表明,miR-204-5p 是 SNHG4 的直接靶标。此外,SNHG4 的敲低抑制了异种移植小鼠模型中的 GC 肿瘤发生。总之,这些数据表明,通过靶向 miR-204-5p,敲低 SNHG4 抑制了 GC 的发展。

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