lncRNA CCAT1 Promotes Glioma Tumorigenesis by Sponging miR-181b
lncRNA CCAT1 Promotes Glioma Tumorigenesis by Sponging miR-181b
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DOI：
10.1002/jcb.26116
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Cui, Youqiang
中科院分区：
文献类型：
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作者：
Cui, Bingzhou;Li, Baoshan;Cui, Youqiang
结肠癌相关转录物1（CCAT1）是一种长链非编码RNA（lncRNA），在许多癌症的发病机制中起着重要作用。近年来发现其在胶质瘤组织中有高表达。miR-181b在胶质瘤中下调，并作为肿瘤抑制因子。然而，CCAT1在神经胶质瘤发展中的调控作用的确切机制仍不清楚。首先通过实时荧光定量PCR检测胶质瘤组织中CCAT1和miR-181b的表达。采用生物信息学分析、CCK-8测定、Transwell测定、流式细胞术、荧光素酶测定、RNA免疫沉淀、实时定量PCR、Western blot和异种移植模型等方法，对CCAT1的表达下调机制进行了分析。在胶质瘤组织中，CCAT1表达显著增加，而miR-181b表达显著减少。有趣的是，在胶质瘤样品中，miR-181b表达与CCAT1水平呈负相关。CCAT1的敲除可显著抑制U87和LN 229胶质瘤细胞的增殖、迁移和上皮-间质转化（EMT）过程，并促进细胞凋亡。此外，我们发现CCAT1可能作为miR-181b的竞争性内源性RNA（ceRNA），调节FGFR 3和PDGFR的去抑制。总之，CCAT1通过海绵状吸收miR-181b促进胶质瘤的发生，导致其内源性靶点FGFR 3和PDGFR的去抑制，这为胶质瘤的治疗提供了潜在的治疗靶点。J.细胞。118：4548 - 4557，2017. (c)2017年Wiley Periodicals，Inc.
Colon cancer-associated transcript 1 (CCAT1), a long non-coding RNA (lncRNA), is upregulated and has a vital role in the pathogenesis of numerous cancers. Recently, its high expression was found in glioma tissues. miR-181b is downregulated in glioma and acts as a tumor suppressor. However, the exact mechanism of CCAT1 action in the regulation of glioma development remains unknown. CCAT1 and miR-181b expression was firstly examined in glioma tissue samples by real-time PCR. An RNA interference approach was used to downregulate CCAT1 expression and we analyzed the underlying mechanism of CCAT1 by using bioinformatics analysis, CCK-8 assay, Transwell assay, flow cytometry, luciferase assay, RNA immunoprecipitation, real-time PCR, Western blot, and xenograft models. CCAT1 expression was significantly increased, while miR-181b decreased, in glioma tissues. Interestingly, miR-181b expression was negatively correlated with the CCAT1 level in glioma samples. Knockdown of CCAT1 notably suppressed proliferation, migration and the epithelial-mesenchymal transition (EMT) process, and promoted the apoptosis of U87 and LN229 glioma cells, which could be enhanced by transfection with miR-181b mimic while it was abolished by anti-miR-181b. Additionally, we found that CCAT1 may act as a competing endogenous RNA (ceRNA) for miR-181b, regulating the de-repression of FGFR3 and PDGFR. In conclusion, CCAT1 promotes glioma tumorigenesis by sponging miR-181b, leading to the de-repression of its endogenous targets FGFR3 and PDGFR, which provides a potential therapeutic target for glioma treatment. J. Cell. Biochem. 118: 4548-4557, 2017. (c) 2017 Wiley Periodicals, Inc.