Department of Endoscopy, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Acupuncture, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Aging (Albany NY). 2020 Apr 4;12(7):6191-6205. doi: 10.18632/aging.103016.
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.
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。