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长链非编码 RNA TPT1-AS1 通过 TPT1-AS1/NF90/VEGFA 信号通路促进结直肠癌的血管生成和转移。

Long non-coding RNA TPT1-AS1 promotes angiogenesis and metastasis of colorectal cancer through TPT1-AS1/NF90/VEGFA signaling pathway.

机构信息

Department of Endoscopy, Harbin Medical University Cancer Hospital, Harbin, China.

Department of Acupuncture, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Aging (Albany NY). 2020 Apr 4;12(7):6191-6205. doi: 10.18632/aging.103016.

Abstract

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.

摘要

LncRNAs 已被证明与肿瘤的进展密切相关。最近的一项研究确定 LncRNA TPT1-AS1(TPT1-AS1)是结直肠癌(CRC)中与肝转移相关的 LncRNA 之一。在这项研究中,我们报告 TPT1-AS1 在 CRC 组织中上调,与预后不良相关。功能分析揭示了 TPT1-AS1 的促血管生成和转移作用。在机制上,Flexmap 3D 分析显示 TPT1-AS1 上调 CRC 细胞中 VEGFA 的分泌。RNA 免疫沉淀和 mRNA 稳定性分析进一步表明,TPT1-AS1 与核因子 90(NF90)相互作用,随后促进 NF90 与 VEGFA mRNA 之间的结合,导致 VEGFA mRNA 稳定性的上调。因此,我们阐明了 TPT1-AS1 在 CRC 血管生成中的新调控机制,靶向 TPT1-AS1/NF90/VEGFA 轴可能为结直肠癌患者的诊断和治疗提供有用的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248a/7185097/abfeeaaddc31/aging-12-103016-g001.jpg

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