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The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression.
- Source :
-
Oncogene [Oncogene] 2013 Sep 12; Vol. 32 (37), pp. 4377-86. Date of Electronic Publication: 2012 Oct 22. - Publication Year :
- 2013
-
Abstract
- Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis whose expression suppresses tumor growth in vivo. Like many angiogenesis-related genes, TSP-1 expression is tightly controlled by various mechanisms, but there is little data regarding the contribution of post-transcriptional processing to this regulation. NOL7 is a novel tumor suppressor that induces an antiangiogenic phenotype and suppresses tumor growth, in part through upregulation of TSP-1. Here we demonstrate that NOL7 is an mRNA-binding protein that must localize to the nucleoplasm to exert its antiangiogenic and tumor suppressive effects. There, it associates with the RNA-processing machinery and specifically interacts with TSP-1 mRNA through its 3'UTR. Reintroduction of NOL7 into SiHa cells increases luciferase expression through interaction with the TSP-1 3'UTR at both the mRNA and protein levels. NOL7 also increases endogenous TSP-1 mRNA half-life. Further, NOL7 post-transcriptional stabilization is observed in a subset of angiogenesis-related mRNAs, suggesting that the stabilization of TSP-1 may be part of a larger novel mechanism. These data demonstrate that NOL7 significantly alters TSP-1 expression and may be a master regulator that coordinates the post-transcriptional expression of key signaling factors critical for the regulation of the angiogenic phenotype.
- Subjects :
- 3' Untranslated Regions
Animals
Cell Line
Cell Nucleus metabolism
Cell Proliferation
Female
Humans
Mice
Neovascularization, Pathologic genetics
Neovascularization, Pathologic metabolism
Phenotype
Protein Binding
RNA, Messenger genetics
RNA, Messenger metabolism
Ribonucleoproteins metabolism
Thrombospondin 1 metabolism
Gene Expression Regulation, Neoplastic
Nuclear Proteins metabolism
RNA Processing, Post-Transcriptional
Thrombospondin 1 genetics
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 32
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 23085760
- Full Text :
- https://doi.org/10.1038/onc.2012.464