Oncotarget

Research Papers:

Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma

Johannes Fänder, Heike Kielstein, Maximilian Büttner, Peter Koelblinger, Reinhard Dummer, Marcus Bauer, Diana Handke, Claudia Wickenhauser, Barbara Seliger and Simon Jasinski-Bergner _

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Oncotarget. 2019; 10:6509-6525. https://doi.org/10.18632/oncotarget.27305

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Abstract

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

Correspondence to:

Simon Jasinski-Bergner,email: simon.jasinski@uk-halle.de

Keywords: CD44; CD44v6; melanoma; microRNA; immune cell infiltration

Received: August 09, 2019     Accepted: October 21, 2019     Published: November 05, 2019

ABSTRACT

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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