Lise M. Lindahl, Maria Gluud, Thomas Emmanuel, Emil A. Thomsen, Tengpeng Hu, Anne H. Rittig, Pamela Celis, Veronica Stolearenco, Thorbjørn Krejsgaard, Claus Johansen, Andreas Willerslev-Olsen, Terkild B. Buus, Anders Woetmann, Lars Aagaard, Carsten Geisler, Thomas Litman, Jacob G. Mikkelsen, Niels Odum, Lars Iversen
DOI: 10.2340/00015555-3574

A prognostic 3-miRNA classifier for early-stage mycosis fungoides has been developed recently, with miR-106b providing the strongest prognostic power. The aim of this study was to investigate the molecular function of miR-106b in mycosis fungoides disease progression. The cellular localization of miR-106b in mycosis fungoides skin biopsies was determined by in situ hybridization. The regulatory role of miR-106b was assessed by transient miR-106b inhibitor/mimic transfection of 2 mycosis fungoides derived cell lines, followed by quantitative real-time PCR (RT-qPCR), western blotting and a proliferation assay. MiR-106b was found to be expressed by dermal T-lymphocytes in mycosis fungoides skin lesions, and miR-106b expression increased with advancing mycosis fungoides stage. Transfection of miR-106b in 2 mycosis fungoides derived cell lines showed that miR-106b represses the tumour suppressors cyclin-dependent kinase inhibitor 1 (p21) and thioredoxin-interacting protein (TXNIP) and promotes mycosis fungoides tumour cell proliferation. In conclusion, these results substantiate that miR-106b has both a functional and prognostic role in progression of mycosis fungoides.

MiR-106b was identified recently as having the strongest prognostic power in a prognostic 3-miRNA classifier developed and validated for early-stage mycosis fungoides. This study provides evidence for miR-106b as a molecular driver of mycosis fungoides disease progression. MiR-106b downregulates the tumour suppressors cyclin-dependent kinase inhibitor 1 (p21) and thioredoxin-interacting protein (TXNIP) and promotes tumour cell proliferation in mycosis fungoides. Thus, miR-106b is both a prognostic marker and a functional driver of disease progression in mycosis fungoides and may serve as a potential new therapeutic target for mycosis fungoides.

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