MicroRNA-106b Regulates Expression of the Tumour Suppressors p21 and TXNIP and Promotes Tumour Cell Proliferation in Mycosis Fungoides

Authors

  • 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:

https://doi.org/10.2340/00015555-3574

Keywords:

mycosis fungoides, cutaneous T-cell lymphoma, microRNA, progression, tumour suppressors, p21, TXNIP

Abstract

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.

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Published

2020-09-30

How to Cite

M. Lindahl, L., Gluud, M., Emmanuel, T., A. Thomsen, E., Hu, T., H. Rittig, A., Celis, P., Stolearenco, V., Krejsgaard, T., Johansen, C., Willerslev-Olsen, A., B. Buus, T., Woetmann, A., Aagaard, L., Geisler, C., Litman, T., G. Mikkelsen, J., Odum, N., & Iversen, L. (2020). MicroRNA-106b Regulates Expression of the Tumour Suppressors p21 and TXNIP and Promotes Tumour Cell Proliferation in Mycosis Fungoides. Acta Dermato-Venereologica, 100(16), 1–8. https://doi.org/10.2340/00015555-3574