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Updated: Oct 15, 2025

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA Isoforms Contribution to Melanoma Pathogenesis
Elisabetta Broseghini1, Emi Dika1,2, Eric Londin3
1Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
Abstract:
Cutaneous melanoma (CM) is the most lethal tumor among skin cancers, and its incidence is constantly increasing. A deeper understanding of the molecular processes guiding melanoma pathogenesis could improve diagnosis, treatment and prognosis. MicroRNAs play a key role in melanoma biology. Recently, next generation sequencing (NGS) experiments, designed to assess small-RNA expression, revealed the existence of microRNA variants with different length and sequence. These microRNA isoforms are known as isomiRs and provide an additional layer to the complex non-coding RNA world. Here, we collected data from NGS experiments to provide a comprehensive characterization of miRNA and isomiR dysregulation in benign nevi (BN) and early-stage melanomas. We observed that melanoma and BN express different and specific isomiRs and have a different isomiR abundance distribution. Moreover, isomiRs from the same microRNA can have opposite expression trends between groups. Using The Cancer Genome Atlas (TCGA) dataset of skin cancers, we analyzed isomiR expression in primary melanoma and melanoma metastasis and tested their association with NF1, BRAF and NRAS mutations. IsomiRs differentially expressed were identified and catalogued with reference to the canonical form. The reported non-random dysregulation of specific isomiRs contributes to the understanding of the complex melanoma pathogenesis and serves as the basis for further functional studies.
Insights
MicroRNA variants called isomiRs are dysregulated in melanoma compared to benign nevi. This finding reveals specific isomiR patterns in cutaneous melanoma (CM) progression and metastasis.
Area of Science:
- Molecular biology
- Cancer research
- Genomics
Background:
- Cutaneous melanoma (CM) is an aggressive skin cancer with increasing incidence.
- MicroRNAs (miRNAs) are crucial in melanoma pathogenesis.
- MicroRNA isoforms (isomiRs) represent a new layer of regulatory complexity.
Purpose of the Study:
- To comprehensively characterize miRNA and isomiR dysregulation in benign nevi (BN) and early-stage melanomas.
- To analyze isomiR expression in primary melanoma versus metastasis using The Cancer Genome Atlas (TCGA) data.
- To investigate the association of isomiR expression with NF1, BRAF, and NRAS mutations in melanoma.
Main Methods:
- Analysis of next-generation sequencing (NGS) data for small-RNA expression.
- Comparison of isomiR profiles between benign nevi and cutaneous melanoma.
- Utilized The Cancer Genome Atlas (TCGA) dataset for melanoma metastasis analysis.
Main Results:
- Benign nevi and melanoma exhibit distinct and specific isomiR expression profiles and abundance distributions.
- IsomiRs derived from the same miRNA can display opposing expression trends between benign nevi and melanoma.
- Differential expression of isomiRs was identified in primary melanoma and metastasis, with associations to specific mutations.
Conclusions:
- Specific isomiRs are non-randomly dysregulated in cutaneous melanoma, contributing to disease pathogenesis.
- IsomiR profiling offers insights into the complex molecular landscape of melanoma.
- Identified isomiRs serve as potential biomarkers for further functional investigation and clinical application.
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