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Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs.
Gabrielle Perron1,2, Pouria Jandaghi2, Elham Moslemi2
1Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada.
Communications Biology
|August 20, 2022
Summary
Cancer progression involves significant mRNA stability changes, impacting tumor development. This study reveals widespread mRNA stability alterations and identifies key RNA-binding proteins and microRNAs driving these cancer-associated shifts.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Measuring messenger RNA (mRNA) decay in tumors is difficult, hindering the understanding of cancer's post-transcriptional regulation.
- Existing methods struggle to distinguish between changes in gene expression and mRNA stability.
Purpose of the Study:
- To develop a statistical framework to differentiate transcriptional and post-transcriptional effects in RNA sequencing data.
- To identify and characterize changes in mRNA stability during tumor development and progression across various cancer types.
Main Methods:
- Utilized a novel statistical framework to analyze RNA-sequencing data from 7760 tumor samples across 18 cancer types.
- Decoupled transcriptional and post-transcriptional regulatory events to specifically assess mRNA stability dynamics.
- Investigated the roles of RNA-binding proteins (RBPs) and microRNAs (miRNAs) implicated in observed stability changes.
Main Results:
- Identified mRNA stability changes as frequent as transcriptional events (~30%) in shaping the tumor transcriptome.
- Discovered dysregulation of pathways involving over 80 RBPs and miRNAs, including inactivation of RBFOX and miR-29 families across multiple cancers.
- Demonstrated RBFOX1's role in calcium signaling and miR-29's impact on extracellular matrix organization and stemness.
Conclusions:
- mRNA stability is a critical, widespread factor in cancer transcriptome regulation, comparable in frequency to transcriptional changes.
- Identified specific RBPs and miRNAs as key drivers of cancer-associated mRNA stability dysregulation.
- Provides a valuable resource for further research into cancer-specific mRNA stability pathways and therapeutic targets.
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