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Updated: May 17, 2026

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
Integrative analysis of somatic mutations altering microRNA targeting in cancer genomes
Jesse D Ziebarth1, Anindya Bhattacharya, Yan Cui
1Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Abstract:
Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in non-coding regions. Here, we study somatic mutations in 3'UTRs of genes that have been identified in four cancers and computationally predict how they may alter miRNA targeting, potentially resulting in dysregulation of the expression of the genes harboring these mutations. We find that somatic mutations create or disrupt putative miRNA target sites in the 3'UTRs of many genes, including several genes, such as MITF, EPHA3, TAL1, SCG3, and GSDMA, which have been previously associated with cancer. We also integrate the somatic mutations with germline mutations and results of association studies. Specifically, we identify putative miRNA target sites in the 3'UTRs of BMPR1B, KLK3, and SPRY4 that are disrupted by both somatic and germline mutations and, also, are in linkage disequilibrium blocks with high scoring markers from cancer association studies. The somatic mutation in BMPR1B is located in a target site of miR-125b; germline mutations in this target site have previously been both shown to disrupt regulation of BMPR1B by miR-125b and linked with cancer.
Insights
Somatic mutations in 3' untranslated regions (UTRs) can alter microRNA (miRNA) targeting, affecting gene expression in cancer. This study reveals how these mutations impact miRNA binding sites, potentially driving tumorigenesis.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Biology
Background:
- Somatic mutations in non-coding regions are increasingly recognized for their role in cancer.
- Understanding the functional impact of these mutations is key to deciphering tumorigenesis and metastasis.
Purpose of the Study:
- To investigate the impact of somatic mutations in 3'UTRs on microRNA (miRNA) targeting and gene expression regulation in four cancer types.
- To identify specific genes and miRNA interactions affected by somatic mutations, and integrate this with germline data and cancer association studies.
Main Methods:
- Computational prediction of miRNA target site alterations due to somatic mutations in 3'UTRs.
- Analysis of somatic mutations across four cancer genomes.
- Integration of somatic mutation data with germline mutations and cancer genome association study results.
Main Results:
- Somatic mutations were found to create or disrupt putative miRNA target sites in the 3'UTRs of numerous genes, including cancer-associated genes like MITF, EPHA3, TAL1, SCG3, and GSDMA.
- Specific genes (BMPR1B, KLK3, SPRY4) showed 3'UTR miRNA target sites disrupted by both somatic and germline mutations, linked to cancer association study markers.
- A somatic mutation in BMPR1B affected a miR-125b target site, mirroring previously observed effects of germline mutations on BMPR1B regulation and cancer linkage.
Conclusions:
- Somatic mutations in 3'UTRs significantly impact miRNA targeting, offering a mechanism for gene dysregulation in cancer.
- The interplay between somatic and germline mutations in miRNA binding sites, particularly in genes like BMPR1B, highlights their combined role in cancer development.
- This research provides insights into the functional consequences of non-coding somatic mutations and their contribution to cancer pathology.
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