Research Paper Volume 12, Issue 7 pp 6191—6205

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

Yiyun Zhang 1, *, , Jiangyun Sun 2, *, , Yuan Qi 3, *, , Yimin Wang 3, , Yu Ding 3, , Kun Wang 4, , Qingxin Zhou 5, , Jingxuan Wang 6, , Fei Ma 3, , Jianguo Zhang 3, , Baoliang Guo 3, ,

  • 1 Department of Endoscopy, Harbin Medical University Cancer Hospital, Harbin, China
  • 2 Department of Acupuncture, The First Affiliated Hospital of Harbin Medical University, Harbin, China
  • 3 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
  • 4 Department of Central Sterile Supply, The First Affiliated Hospital of Harbin Medical University, Harbin, China
  • 5 Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China
  • 6 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
* Equal contribution

received: October 27, 2019 ; accepted: February 25, 2020 ; published: April 4, 2020 ;

https://doi.org/10.18632/aging.103016
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

Lnc TPT1-AS1: long non-coding RNA TPT1-AS1; TCGA: the cancer genome atlas; CRC: colorectal cancer; NF90: nuclear factor 90; VEGFA: the vascular endothelial growth factor A; RIP: RNA immunoprecipitation; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; RBP: RNA-binding protein.