Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma
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Johannes Fänder1, Heike Kielstein1, Maximilian Büttner1, Peter Koelblinger2, Reinhard Dummer3, Marcus Bauer4, Diana Handke5, Claudia Wickenhauser4, Barbara Seliger5 and Simon Jasinski-Bergner1,5
1 Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany
2 Department of Dermatology, Paracelsus Medical University, Salzburg, Austria
3 Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland
4 Institute for Pathology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany
5 Institute for Medical Immunology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany
Keywords: CD44; CD44v6; melanoma; microRNA; immune cell infiltration
Received: August 09, 2019 Accepted: October 21, 2019 Published: November 05, 2019
The multistructural and multifunctional transmembrane glycoprotein CD44 is overexpressed in many tumors of distinct origin including malignant melanoma and contributes to a poor prognosis by affecting cell proliferation, cell migration, and also the sensitivity for apoptosis induction. Previous studies reported so far 15 CD44 regulatory microRNAs (miRs) in different cell systems.
Using a novel method for miR affinity purification miR-143-3p was identified as most potent binder to the 3’ untranslated region (UTR) of CD44. Overexpression of miR-143-3p in melanoma cells inhibits CD44 translation, which is accompanied by a reduced proliferation, migration and enhanced daunorubicin induced apoptosis of melanoma cells in vitro.
Analyses of discordant CD44 and miR-143-3p expression levels in human melanocytic nevi and dermal melanoma samples demonstrated medium to high CD44 levels with no association to tumor grading or staging. The CD44 expression correlated to PD-L1, but not to MART-1 expression in malignant melanoma. Interestingly, the CD44 expression was inversely correlated to the infiltration of pro-inflammatory immune effector cells.
In conclusion, the tumor suppressive miR-143-3p was identified as the most potent CD44 inhibitory miR, which affects growth characteristics of melanoma cells suggesting the implementation of miR-143-3p as as a potential anti-CD44 therapy of malignant melanoma.
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