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miR-184 represses β-catenin and behaves as a skin tumor suppressor

Lubov Turovsky1,2, Ghazal Kheshaiboun1,2, Gharam Yassen1

  • 1Department of Genetics & Developmental Biology, The Rappaport Faculty of Medicine & Research Institute, Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, 31096, Israel.

Cell Death & Disease
|February 26, 2024
PubMed

Insights

MicroRNA-184 (miR-184) acts as a tumor suppressor in the skin. Its absence promotes skin cancer development by affecting stem cell dynamics and increasing beta-catenin levels.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Oncology

Background:

  • MicroRNA-184 (miR-184) is implicated in epidermal stem cell differentiation.
  • The role of miR-184 in skin pathology, particularly skin cancer, remains largely undefined.

Purpose of the Study:

  • To investigate the function of miR-184 in epidermal stem cell dynamics.
  • To determine the role of miR-184 in skin carcinogenesis and squamous cell carcinoma (SCC) development.

Main Methods:

  • Utilized miR-184 knockout mice to study epidermal stem cell differentiation and skin carcinogenesis.
  • Assessed the impact of miR-184 repression on human SCC cells in vitro and in vivo.
  • Analyzed the miR-184 regulatory network and its effect on pro-oncogenic pathways, including beta-catenin signaling.

Main Results:

  • miR-184 knockout mice exhibited disrupted epidermal stem cell differentiation and enhanced skin carcinogenesis.
  • Repression of miR-184 in human SCC cells promoted neoplastic characteristics and tumor growth.
  • miR-184 was found to inhibit pro-oncogenic pathways, cell proliferation, and epithelial-mesenchymal transition.
  • miR-184 depletion led to increased beta-catenin levels, and its repression of beta-catenin inhibited the SCC neoplastic phenotype.

Conclusions:

  • miR-184 functions as an epidermal tumor suppressor.
  • miR-184 plays a critical role in controlling epidermal stem cell homeostasis and preventing skin cancer.
  • miR-184 represents a potential therapeutic target for skin squamous cell carcinoma.

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