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miRNA Combinatorics and its Role in Cell State Control-A Probabilistic Approach
Shelly Mahlab-Aviv1, Nathan Linial1, Michal Linial2
1The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Frontiers in Molecular Biosciences
|January 7, 2022
Summary
Altering microRNA (miRNA) composition can significantly shift cell identity and impact cancer evolution. Our study shows abundant miRNAs dictate cell behavior, regardless of mRNA levels, highlighting a quantitative regulatory dimension.
Area of Science:
- Molecular Biology
- Cancer Research
- Computational Biology
Background:
- Cancer evolution involves dynamic changes in cell identity and fitness.
- MicroRNA (miRNA) composition changes significantly during these dynamic processes.
- Cellular averaging in cancer samples masks cell-specific molecular profiles.
Purpose of the Study:
- To investigate how altering miRNA composition affects cell behavior.
- To explore the quantitative dimension of miRNA regulation in living cells.
- To understand the impact of miRNA perturbations on cell identity and cancer evolution.
Main Methods:
- Utilized COMICS, an iterative computational framework simulating miRNA-mRNA pairing.
- Employed a probabilistic approach to model stochastic gene expression events.
- Performed *in silico* perturbations (miRNA overexpression) on human cell lines (HeLa).
Main Results:
- Confirmed most genes are resistant to miRNA regulation.
- Demonstrated that abundant miRNA composition dictates cell nature, irrespective of mRNA steady-state.
- Classified genes based on sensitivity and resilience to miRNA perturbations.
Conclusions:
- Revealed an overlooked quantitative aspect of miRNA and gene regulation.
- Showed that modest miRNA overexpression can alter cell identity.
- Highlighted the potential for miRNA modulation to impact cancer evolution.
Keywords:
CLIP-SeqMarkov chainTargetScanceRNAcell linecell simulationmiRNA binding sitemiRNA-target predictionMore Related Videos
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