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长链非编码 RNA TNRC6C-AS1 通过作为 miR-129-5p 的竞争性内源 RNA 调控甲状腺癌细胞中的 UNC5B 影响细胞增殖、迁移和侵袭。

LncRNA TNRC6C-AS1 regulates UNC5B in thyroid cancer to influence cell proliferation, migration, and invasion as a competing endogenous RNA of miR-129-5p.

机构信息

Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun, Jilin, China.

出版信息

J Cell Biochem. 2018 Nov;119(10):8304-8316. doi: 10.1002/jcb.26868. Epub 2018 Jun 12.

DOI:10.1002/jcb.26868
PMID:29893424
Abstract

To investigate the biological functions and regulatory mechanism of lncRNA TNRC6C-AS1 in thyroid cancer (TC). TNRC6C-AS1, miR-129-5p, and UNC5B expression levels were investigated by qRT-PCR and Western blot. CCK-8 assay was conducted to determine cell proliferation, while transwell assay was for inspection of cell migration and invasion. Through bioinformatic analysis, the interactions among TNRC6C-AS1, miR-129-5p, and UNC5B were predicted. Dual luciferase reporter gene assay and RNA pull-down assay confirmed the predicted target relationships. Tumor xenograft assay was applied to inspect the effect of TNRC6C-AS1 downregulation on TC development in vivo. TNRC6C-AS1 and UNC5B were overexpressed, while miR-129-5p was underexpressed in TC tissues and cells. TNRC6C-AS1/UNC5B downregulation and miR-129-5p overexpression could suppress proliferation, migration, and invasion of TC cells as well as inhibit tumorigenesis in vivo. MiR-129-5p targeted TNRC6C-AS1 and UNC5B in TC cells; and UNC5B expression was downregulated by knocking down TNRC6C-AS1, which competitively bound with miR-129-5p. Downregulation of TNRC6C-AS1 restrained TC development by knocking down UNC5B through upregulating the expression of miR-129-5p.

摘要

为了研究长链非编码 RNA(lncRNA)TNRC6C-AS1 在甲状腺癌(TC)中的生物学功能和调控机制。采用 qRT-PCR 和 Western blot 检测 TNRC6C-AS1、miR-129-5p 和 UNC5B 的表达水平。通过 CCK-8 测定法检测细胞增殖,Transwell 测定法检测细胞迁移和侵袭。通过生物信息学分析,预测了 TNRC6C-AS1、miR-129-5p 和 UNC5B 之间的相互作用。双荧光素酶报告基因检测和 RNA 下拉实验验证了预测的靶关系。肿瘤异种移植实验用于检测 TNRC6C-AS1 下调对 TC 体内发展的影响。在 TC 组织和细胞中,TNRC6C-AS1 和 UNC5B 过表达,而 miR-129-5p 低表达。TNRC6C-AS1/UNC5B 下调和 miR-129-5p 过表达可抑制 TC 细胞的增殖、迁移和侵袭,并抑制体内肿瘤发生。miR-129-5p 在 TC 细胞中靶向 TNRC6C-AS1 和 UNC5B;敲低 TNRC6C-AS1 可下调 UNC5B 的表达,其与 miR-129-5p 竞争结合。下调 TNRC6C-AS1 通过上调 miR-129-5p 的表达来抑制 TC 的发展。

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