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长链非编码 RNA CTC 通过靶向 miR-146 调控 KIT 抑制甲状腺乳头状癌的增殖和侵袭。

Long Noncoding RNA CTC Inhibits Proliferation and Invasion by Targeting miR-146 to Regulate KIT in Papillary Thyroid Carcinoma.

机构信息

Department of Thyroid Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Scicences, Wuhan University, Wuhan, 430072, China.

出版信息

Sci Rep. 2020 Mar 12;10(1):4616. doi: 10.1038/s41598-020-61577-z.

Abstract

Several lines of evidence have shown that long non-coding RNAs (lncRNAs) are dysregulated in many diseases. Nevertheless, the biological relevance of the lncRNAs in papillary thyroid carcinoma (PTC) has not been fully explored. We demonstrated that CTC was a negative regulator of PTC cell migration and invasion in vitro and in vivo. We found that microRNA-146 (miR-146) is an inhibitory target of CTC. We then demonstrated that CTC functioned as a miR-146 decoy to de-repress expression of KIT. Further study demonstrated that CTC modulated the progression and chemoresistance of PTC cells via miR-146 and KIT. The analysis of hundreds of clinical specimens revealed that CTC and KIT levels were downregulated, whereas miR-146 levels were greater in PTC tissues than in normal thyroid. Their expression levels correlated with one another. In conclusion, CTC functions as a competing endogenous RNA to inhibit the progression and chemoresistance of PTC cells, and identifies CTC serve as a potential therapeutic agent to suppress PTC progression.

摘要

有几条证据表明,长链非编码 RNA(lncRNAs)在许多疾病中失调。然而,lncRNAs 在甲状腺乳头状癌(PTC)中的生物学相关性尚未得到充分探索。我们证明 CTC 在体外和体内是 PTC 细胞迁移和侵袭的负调节剂。我们发现 microRNA-146(miR-146)是 CTC 的抑制性靶标。然后我们证明 CTC 作为 miR-146 诱饵发挥作用,解除 KIT 的表达抑制。进一步的研究表明,CTC 通过 miR-146 和 KIT 调节 PTC 细胞的进展和化疗耐药性。对数百份临床标本的分析表明,CTC 和 KIT 水平下调,而 PTC 组织中的 miR-146 水平高于正常甲状腺。它们的表达水平相互关联。总之,CTC 作为竞争性内源性 RNA 发挥作用,抑制 PTC 细胞的进展和化疗耐药性,并确定 CTC 可作为抑制 PTC 进展的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9f0/7067803/ad29d8aca97e/41598_2020_61577_Fig1_HTML.jpg

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