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An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
Analysis of microRNA-target interactions across diverse cancer types
Anders Jacobsen1, Joachim Silber, Girish Harinath
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Abstract:
Little is known about the extent to which individual microRNAs (miRNAs) regulate common processes of tumor biology across diverse cancer types. Using molecular profiles of >3,000 tumors from 11 human cancer types in The Cancer Genome Atlas, we systematically analyzed expression of miRNAs and mRNAs across cancer types to infer recurrent cancer-associated miRNA-target relationships. As we expected, the inferred relationships were consistent with sequence-based predictions and published data from miRNA perturbation experiments. Notably, miRNAs with recurrent target relationships were frequently regulated by genetic and epigenetic alterations across the studied cancer types. We also identify new examples of miRNAs that coordinately regulate cancer pathways, including the miR-29 family, which recurrently regulates active DNA demethylation pathway members TET1 and TDG. The online resource http://cancerminer.org allows exploration and prioritization of miRNA-target interactions that potentially regulate tumorigenesis.
Insights
This study reveals how microRNAs (miRNAs) impact tumor biology across many cancers. It identifies key miRNA-target interactions and their regulation, offering insights into cancer development.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- The role of individual microRNAs (miRNAs) in regulating shared tumor biology processes across diverse cancer types remains largely unknown.
- Understanding these regulatory networks is crucial for advancing cancer research and therapy.
Purpose of the Study:
- To systematically analyze miRNA and messenger RNA (mRNA) expression across multiple human cancer types.
- To infer recurrent cancer-associated miRNA-target relationships and identify novel regulatory interactions.
- To provide a resource for exploring and prioritizing miRNA-target interactions in tumorigenesis.
Main Methods:
- Utilized molecular profiles from over 3,000 tumors across 11 human cancer types from The Cancer Genome Atlas (TCGA).
- Performed systematic analysis of miRNA and mRNA expression to infer miRNA-target relationships.
- Validated inferred relationships against sequence-based predictions and experimental data.
Main Results:
- Identified recurrent miRNA-target relationships consistent with existing knowledge and predictions.
- Found that miRNAs with recurrent targets are frequently regulated by genetic and epigenetic alterations in cancer.
- Discovered new examples of miRNAs coordinating cancer pathways, such as the miR-29 family regulating DNA demethylation (TET1, TDG).
Conclusions:
- Established a framework for understanding miRNA regulation in pan-cancer tumor biology.
- Highlighted the significance of genetic and epigenetic alterations in modulating miRNA activity in cancer.
- Developed an online resource (http://cancerminer.org) to facilitate the study of miRNA-target interactions in cancer.
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