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MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as A Novel Detection and Quantification Method
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Targeting the microbiota-miRNA-protease axis: A new therapeutic avenue in melanoma

Elias N Katsoulieris1, Paraskevi Ioannou1, Nikolaos A Afratis1,2

  • 1Laboratory of Biotechnology and Molecular Analysis, Department of Agricultural Development, Agri-food & Management of Natural Resources, National and Kapodistrian University of Athens, Evia, Greece.

The FEBS Journal
|January 8, 2026
PubMed

Insights

This review explores how microRNAs (miRNAs) regulate extracellular matrix (ECM) proteases, impacting melanoma metastasis. It also examines the link between gut microbiota, miRNAs, and melanoma progression, suggesting novel therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Melanoma metastasis is critically dependent on the modulation of extracellular matrix (ECM) turnover.
  • ECM proteases play a key role in ECM degradation, influencing melanoma cell growth, migration, invasion, and immune evasion.
  • Complex transcriptional and post-transcriptional regulatory mechanisms control ECM protease activity during melanoma progression.

Purpose of the Study:

  • To review the role of epigenetic machinery, specifically microRNAs (miRNAs), in targeting ECM protease transcripts.
  • To examine the influence of gut dysbiosis on miRNA profiles and its link to melanoma progression and immunotherapy resistance.
  • To evaluate the therapeutic potential of targeting ECM proteases and modulating gut microbiota for melanoma treatment.

Main Methods:

  • Literature review focusing on epigenetic regulation of ECM proteases by miRNAs in melanoma.
  • Analysis of studies linking gut microbiota dysbiosis to altered miRNA expression and melanoma progression.
  • Evaluation of therapeutic strategies involving miRNA targeting and gut microbiota modulation.

Main Results:

  • MicroRNAs directly target ECM protease transcripts, significantly influencing melanoma cell behavior and progression.
  • Gut dysbiosis is associated with altered matrix metalloproteinase-targeting miRNA profiles, contributing to melanoma resistance to immunotherapy.
  • Modulation of gut microbiota and direct miRNA targeting show promise as adjuvant therapies for melanoma.

Conclusions:

  • Epigenetic regulation by miRNAs is a crucial factor in melanoma metastasis via ECM protease modulation.
  • The gut microbiome influences melanoma progression and immunotherapy response through miRNA-mediated pathways.
  • Combined strategies targeting gut microbiota and ECM proteases via miRNAs offer innovative therapeutic avenues for melanoma.
Keywords:
extracellular matrixgut microbiotaimmune checkpoint inhibitorsinflammatory responsematrix metalloproteinasesmelanomamiRNAproteases

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