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长链非编码 RNA AB074169 通过调节 KHSRP 介导的 CDKN1a 表达抑制甲状腺乳头状癌细胞增殖。

Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma.

机构信息

Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, China.

Department of Head and Neck Cancer, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Cancer Res. 2018 Aug 1;78(15):4163-4174. doi: 10.1158/0008-5472.CAN-17-3766. Epub 2018 May 7.

Abstract

Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition and , whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma. http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg .

摘要

长链非编码 RNA(lncRNA)作为与肿瘤发生相关的基因表达的新型调控因子而出现。然而,lncRNA 在甲状腺乳头状癌(PTC)中的作用尚不清楚。在这里,我们进行了全局 lncRNA 分析,发现 lncRNA AB074169(lncAB)在 PTC 中显著下调。PTC 中 lncAB 的表达下调是由其基因启动子内的 CpG 过度甲基化引起的。功能研究表明,lncAB 的过表达导致细胞周期停滞和肿瘤生长抑制,而 lncAB 的敲低则促进细胞增殖。机制分析表明,lncAB 结合 KH 型剪接调节蛋白(KHSRP),并降低 KHSRP 的表达,从而增加 CDKN1a(p21)的表达并降低 CDK2 的表达,从而抑制细胞增殖。总之,这些发现表明 lncAB 在 PTC 肿瘤发生过程中作为肿瘤抑制因子发挥作用。这些发现确定了甲状腺乳头状癌中的一种肿瘤抑制性长链非编码 RNA。

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