The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5.
The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5.
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lncRNA NEAT1 激活 Wnt/β-catenin 信号传导，并通过与 DDX5 相互作用促进结直肠癌进展。
DOI：
10.1186/s13045-018-0656-7
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发表时间：
2018-09-05
影响因子：
28.5
通讯作者：
Du X
中科院分区：
文献类型：
--
作者：
Zhang M;Weng W;Zhang Q;Wu Y;Ni S;Tan C;Xu M;Sun H;Liu C;Wei P;Du X
长非编码核富含转录本1(NEAT1)在结直肠癌中高表达。然而，其在结直肠癌发展过程中的潜在机制尚未得到很好的研究。为了研究NEAT1的临床意义，我们分析了NEAT1在公开可用的数据集和复旦大学上海肿瘤中心71例大肠癌标本中的表达水平。功能分析，包括CCK8、EDU、集落形成、伤口愈合和Transwell试验，用于确定NEAT1在人类结直肠癌进展中的致癌作用。此外，利用RNA下拉、质谱仪、RNA免疫沉淀和双荧光素酶报告分析来确定NEAT1在结直肠癌进展中的作用机制。动物实验确定NEAT1在体内结直肠癌发生和转移中的作用。与正常组织相比，NEAT1在结直肠癌组织中的表达显著上调。在体外和体内，NEAT1表达的改变导致了结直肠癌细胞的增殖、迁移和侵袭的显著变化。在机制上，我们发现NEAT1直接与DDX5蛋白结合，调节其稳定性，并随后激活Wnt信号。我们的研究表明，NEAT1通过DDX5间接激活Wnt/β-catenin信号通路，并以DDX5介导的方式完成其致癌功能。临床上，伴随的NEAT1和DDX5蛋白水平与结直肠癌患者的总体生存期和无病生存期呈负相关。我们的研究结果表明，NEAT1激活了Wnt信号，促进了结直肠癌的进展和转移。NEAT1/DDX5/Wnt/β-catenin轴可能成为潜在的药物治疗靶点。本文的在线版本(10.1186/s130450180656-7)包含补充材料，授权用户可以使用。
The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo. NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients. Our findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies. The online version of this article (10.1186/s13045-018-0656-7) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
Li Y;Li Y;Chen W;He F;Tan Z;Zheng J;Wang W;Zhao Q;Li J
通讯作者：
Li J
影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1186/s13058-014-0496-5
发表时间：
2014-12-12
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
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通讯作者：
Ghosh MK