MicroRNA-106b Regulates Expression of the Tumour Suppressors p21 and TXNIP and Promotes Tumour Cell Proliferation in Mycosis Fungoides
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
Preview of fully accepted paper, still not published in any volume
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.