Related Experiment Video
Updated: May 17, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression
1Departments of Pathology, Medicine and Radiation, and Cellular Oncology, University of Chicago, Chicago, IL, USA.
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.
Insights
NOL7, a novel tumor suppressor, enhances antiangiogenic effects by stabilizing thrombospondin-1 (TSP-1) mRNA. This regulation occurs via nucleoplasmic localization and interaction with TSP-1 mRNA, suggesting a new mechanism for controlling angiogenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Thrombospondin-1 (TSP-1) inhibits angiogenesis and tumor growth.
- Post-transcriptional regulation of TSP-1 is not well understood.
- NOL7 is a novel tumor suppressor that upregulates TSP-1.
Purpose of the Study:
- To investigate the role of NOL7 in TSP-1 regulation.
- To elucidate the mechanism by which NOL7 exerts its antiangiogenic and tumor suppressive effects.
- To determine if NOL7 impacts post-transcriptional processing of TSP-1 mRNA.
Main Methods:
- Demonstrated NOL7 as an mRNA-binding protein.
- Localized NOL7 to the nucleoplasm for its function.
- Showed NOL7 associates with RNA-processing machinery.
- Identified specific interaction of NOL7 with TSP-1 mRNA 3'UTR.
- Measured luciferase expression and mRNA half-life in SiHa cells.
Main Results:
- NOL7 requires nucleoplasmic localization for antiangiogenic and tumor suppressive effects.
- NOL7 directly interacts with TSP-1 mRNA's 3'UTR.
- NOL7 increases TSP-1 mRNA half-life and protein levels.
- NOL7 also stabilizes other angiogenesis-related mRNAs post-transcriptionally.
Conclusions:
- NOL7 is a nucleoplasmic mRNA-binding protein that stabilizes TSP-1 mRNA.
- NOL7 may act as a master regulator coordinating post-transcriptional expression of angiogenesis factors.
- This study reveals a novel mechanism of angiogenesis regulation involving NOL7 and TSP-1 mRNA stabilization.
More Related Videos
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
02:55The Nucleolus