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

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

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.

Keywords: LncRNA TPT1-AS1; NF90; VEGFA; angiogenesis; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor* / metabolism
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Metastasis* / genetics
  • Neovascularization, Pathologic* / genetics
  • Nuclear Factor 90 Proteins / metabolism
  • RNA, Antisense*
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction
  • Tumor Protein, Translationally-Controlled 1
  • Up-Regulation
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Biomarkers, Tumor
  • Nuclear Factor 90 Proteins
  • RNA, Long Noncoding
  • TPT1 protein, human
  • Tumor Protein, Translationally-Controlled 1
  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human
  • RNA, Antisense