Long non-coding RNA TPT1-AS1 promotes angiogenesis and metastasis of colorectal cancer through TPT1-AS1/NF90/VEGFA signaling pathway
Long non-coding RNA TPT1-AS1 promotes angiogenesis and metastasis of colorectal cancer through TPT1-AS1/NF90/VEGFA signaling pathway
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长非编码RNA TPT1-AS1通过TPT1-AS1/NF90/VEGFA信号通路促进结直肠癌血管生成和转移
DOI：
10.18632/aging.103016
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发表时间：
2020-04-15
期刊：
影响因子：
5.2
通讯作者：
Guo, Baoliang
中科院分区：
文献类型：
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作者：
Zhang, Yiyun;Sun, Jiangyun;Guo, Baoliang
LncRNA已被证明与肿瘤进展密切相关。最近的一项研究将LncRNA TPT 1-AS 1（TPT 1-AS 1）鉴定为结直肠癌（CRC）中肝转移相关的LncRNA之一。在这项研究中，我们报告TPT 1-AS 1在结直肠癌组织中上调，这与预后不良有关。功能测定揭示了TPT 1-AS 1的促血管生成和转移作用。从机制上讲，Flexmap 3D测定揭示了TPT 1-AS 1上调CRC细胞中的VEGFA分泌。RNA免疫沉淀和mRNA稳定性分析进一步表明，TPT 1-AS 1与核因子90（NF 90）相互作用，随后促进NF 90和VEGFA mRNA之间的关联，这导致VEGFA mRNA稳定性上调。因此，我们阐明了TPT 1-AS 1在结直肠癌血管生成中的新的调控机制，靶向TPT 1-AS 1/NF 90/VEGFA轴可能为结直肠癌患者的诊断和治疗提供有用的策略。
LncRNAs have been proven closely correlated to tumor progression. A recent study identified LncRNA TPT1-AS1 (TPT1-AS1) as one of the liver-metastasis associated LncRNAs in colorectal cancer (CRC). In this study, we report that TPT1-AS1 is upregulated in CRC tissues, which is associated with poor prognosis. Functional assays unravel a pro-angiogenesis and metastasis role of TPT1-AS1. Mechanistically, Flexmap 3D assays reveal that TPT1-AS1 upregulates the VEGFA secretion in CRC cells. RNA immunoprecipitation and mRNA stability assays further show that TPT1-AS1 interacts with nuclear factor 90 (NF90) and subsequently promotes the association between NF90 and VEGFA mRNA, which leads to the upregulation of VEGFA mRNA stability. Therefore, we elucidate a new regulatory mechanism of TPT1-AS1 in CRC angiogenesis and targeting the TPT1-AS1/NF90/VEGFA axis may provide a useful strategy for diagnosis and treatment for colorectal cancer patients.