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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival
Yu-Chiao Chiu1,2,3, Li-Ju Wang3, Tzu-Pin Lu4
1Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Background:
Recent studies illuminated a novel role of microRNA (miRNA) in the competing endogenous RNA (ceRNA) interaction: two genes (ceRNAs) can achieve coexpression by competing for a pool of common targeting miRNAs. Individual biological investigations implied ceRNA interaction performs crucial oncogenic/tumor suppressive functions in glioblastoma multiforme (GBM). Yet, a systematic analysis has not been conducted to explore the functional landscape and prognostic significance of ceRNA interaction.
Results:
Incorporating the knowledge that ceRNA interaction is highly condition-specific and modulated by the expressional abundance of miRNAs, we devised a ceRNA inference by differential correlation analysis to identify the miRNA-modulated ceRNA pairs. Analyzing sample-paired miRNA and gene expression profiles of GBM, our data showed that this alternative layer of gene interaction is essential in global information flow. Functional annotation analysis revealed its involvement in activated processes in brain, such as synaptic transmission, as well as critical tumor-associated functions. Notably, a systematic survival analysis suggested the strength of ceRNA-ceRNA interactions, rather than expressional abundance of individual ceRNAs, among three immune response genes (CCL22, IL2RB, and IRF4) is predictive of patient survival. The prognostic value was validated in two independent cohorts.
Conclusions:
This work addresses the lack of a comprehensive exploration into the functional and prognostic relevance of ceRNA interaction in GBM. The proposed efficient and reliable method revealed its significance in GBM-related functions and prognosis. The highlighted roles of ceRNA interaction provide a basis for further biological and clinical investigations.
Insights
MicroRNA (miRNA) interactions, known as competing endogenous RNA (ceRNA) networks, play a role in glioblastoma multiforme (GBM). The strength of ceRNA interactions among immune genes predicts patient survival, offering new insights into GBM prognosis.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- MicroRNAs (miRNAs) regulate gene expression through competing endogenous RNA (ceRNA) interactions.
- ceRNA networks are implicated in glioblastoma multiforme (GBM) oncogenesis and tumor suppression.
- A systematic analysis of ceRNA functional landscape and prognostic significance in GBM is lacking.
Purpose of the Study:
- To systematically explore the functional landscape of ceRNA interactions in GBM.
- To investigate the prognostic significance of ceRNA interactions in GBM.
- To develop an efficient method for inferring miRNA-modulated ceRNA pairs.
Main Methods:
- Devised a ceRNA inference method using differential correlation analysis.
- Analyzed sample-paired miRNA and gene expression profiles of GBM.
- Performed functional annotation and systematic survival analysis.
Main Results:
- Identified miRNA-modulated ceRNA pairs essential for global information flow in GBM.
- Revealed ceRNA involvement in brain-specific functions like synaptic transmission and tumor-associated functions.
- Demonstrated that ceRNA interaction strength among immune genes (CCL22, IL2RB, IRF4) predicts patient survival, validated in independent cohorts.
Conclusions:
- Addressed the lack of comprehensive exploration of ceRNA interactions in GBM.
- Developed an efficient and reliable method to reveal ceRNA significance in GBM functions and prognosis.
- Highlighted the prognostic value of ceRNA interactions, providing a basis for further research.
