Related Experiment Video
Updated: May 15, 2026

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Multiple functions of a glioblastoma fusion oncogene
1Ludwig Institute for Cancer Research, UCSD, La Jolla, California, USA.
Abstract:
RNA sequencing facilitates the discovery of novel gene fusions in cancer. In this issue of the JCI, Parker et al. identify an FGFR3-TACC3 fusion oncogene in glioblastoma and demonstrate a novel mechanism of pathogenicity. A miR-99a binding site within the 3'-untranslated region (3'-UTR) of FGFR3 is lost, releasing FGFR3 signaling from miR-99a-dependent inhibition and greatly enhancing tumor progression relative to WT FGFR3. These results provide compelling insight into the pathogenicity of a novel fusion oncogene and suggest new therapeutic approaches for a subset of glioblastomas.
Insights
Researchers discovered a new FGFR3-TACC3 fusion oncogene in glioblastoma. Loss of a miR-99a binding site enhances tumor progression, offering potential new therapeutic targets for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gene fusions are increasingly recognized as drivers of cancer.
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- MicroRNAs play crucial roles in regulating gene expression and cellular processes.
Purpose of the Study:
- To identify novel gene fusions in glioblastoma using RNA sequencing.
- To elucidate the mechanism of pathogenicity for identified fusion oncogenes.
- To explore potential therapeutic strategies targeting these novel oncogenic drivers.
Main Methods:
- RNA sequencing was employed to detect gene fusions in glioblastoma samples.
- Functional assays were performed to assess the impact of the FGFR3-TACC3 fusion on cellular signaling.
- Analysis of microRNA binding sites and their role in regulating gene expression was conducted.
Main Results:
- An FGFR3-TACC3 fusion oncogene was identified in glioblastoma.
- The fusion results in the loss of a miR-99a binding site in the 3'-untranslated region of FGFR3.
- This loss abrogates miR-99a-mediated inhibition, leading to enhanced FGFR3 signaling and accelerated tumor progression compared to wild-type FGFR3.
Conclusions:
- The FGFR3-TACC3 fusion represents a novel oncogenic driver in a subset of glioblastomas.
- The disruption of miR-99a regulation is a key mechanism contributing to the pathogenicity of this fusion.
- Targeting the aberrant FGFR3 signaling pathway presents a promising therapeutic avenue for glioblastoma patients harboring this fusion.
More Related Videos
12:52Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
07:39Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions
Published on: November 17, 2021
Related Concept Videos
Cancer-Critical Genes I: Proto-oncogenes
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...
Cancer-Critical Genes I: Proto-oncogenes
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...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Induced Pluripotent Stem Cells
Somatic cells are...
The Ras Gene
Ras is a superfamily...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...