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Updated: Mar 18, 2026
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Co-Expression Network Analysis of Fbxw7-Associated LncRNAs Reveals Their Functions in Radiation-Induced Thymic
Antoine M Snijders1, Jian-Hua Mao1
1Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Abstract:
FBXW7, an E3-ubiquitin protein ligase in SCFs (SKP1-cullin-F-box) complex, is a major human tumor suppressor gene, and understanding mechanisms by which FBXW7 contributes to tumorigenesis is critical for the treatment of human cancers with FBXW7 deficiency. Long non-coding RNAs (lncRNAs) have emerged as key regulators of various biological processes. Here we have identified a set of lncRNAs that are associated with Fbxw7 deficiency. The correlation network and functional annotation analysis revealed that Fbxw7-associated lncRNAs regulate genes involved in cell cycle, DNA repair, metabolic process, and cell communication and adhesion. The number of coding genes that correlated with individual lncRNAs varied largely. A lncRNA on chromosome 15 (A_30_P01032978), which was upregulated in tumors from Fbxw7 deficient mice was positively correlated with 15 coding genes. High expression of this 15-gene signature was associated with poor prognosis in two independent human breast cancer studies. Our results open possible new avenues to understand mechanisms by which Fbxw7 deficiency increases tumor susceptibility via the alteration of lncRNAs.
Insights
FBXW7, a tumor suppressor gene, interacts with long non-coding RNAs (lncRNAs) in cancer. A specific lncRNA signature linked to FBXW7 deficiency correlates with poor prognosis in breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- FBXW7 is a crucial human tumor suppressor gene within the SCF (SKP1-cullin-F-box) complex.
- Understanding FBXW7's role in tumorigenesis is vital for treating cancers with FBXW7 deficiency.
- Long non-coding RNAs (lncRNAs) are recognized as key regulators in diverse biological processes.
Purpose of the Study:
- To identify long non-coding RNAs (lncRNAs) associated with FBXW7 deficiency.
- To investigate the functional roles of these lncRNAs in cancer development.
- To explore the prognostic significance of FBXW7-associated lncRNAs in human cancers.
Main Methods:
- Identification of lncRNAs correlated with FBXW7 deficiency.
- Correlation network and functional annotation analysis of associated lncRNAs.
- Analysis of a specific lncRNA signature in human breast cancer datasets.
Main Results:
- A set of lncRNAs associated with FBXW7 deficiency was identified.
- These lncRNAs regulate genes involved in cell cycle, DNA repair, metabolism, and cell adhesion.
- A 15-gene signature linked to an upregulated lncRNA (A_30_P01032978) in FBXW7-deficient tumors predicted poor prognosis in breast cancer patients.
Conclusions:
- FBXW7 deficiency alters the landscape of lncRNAs, impacting key cellular processes.
- FBXW7-associated lncRNAs represent potential biomarkers for cancer prognosis.
- These findings offer new insights into how FBXW7 deficiency contributes to tumor susceptibility through lncRNA dysregulation.
