MiR-125b, a MicroRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2

Ning Xu, Petter Brodin, Tianling Wei, Florian Meisgen, Liv Eidsmo, N. Nagy, L. Kemény, Mona Ståhle, Enikö Sonkoly, Andor Pivarcsi

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in the regulation of gene expression. We previously identified a characteristic miRNA expression profile in psoriasis, distinct from that of healthy skin. One of the most downregulated miRNAs in psoriasis skin was microRNA-125b (miR-125b). In this study, we aimed to identify the potential role(s) of miR-125b in psoriasis pathogenesis. In situ hybridization results showed that the major cell type responsible for decreased miR-125b levels in psoriasis lesions was the keratinocyte. Overexpression of miR-125b in primary human keratinocytes suppressed proliferation and induced the expression of several known differentiation markers. Conversely, inhibition of endogenous miR-125b promoted cell proliferation and delayed differentiation. Fibroblast growth factor receptor 2 (FGFR2) was identified as one of the direct targets for suppression by miR-125b by luciferase reporter assay. The expression of miR-125b and FGFR2 was inversely correlated in both transfected keratinocytes and in psoriatic skin. Knocking down FGFR2 expression by siRNA suppressed keratinocyte proliferation, but did not enhance differentiation. Altogether, our results demonstrate a role for miR-125b in the regulation of keratinocyte proliferation and differentiation, partially through the regulation of FGFR2. Loss of miR-125b in psoriasis skin may contribute to hyperproliferation and aberrant differentiation of keratinocytes.

Original languageEnglish
Pages (from-to)1521-1529
Number of pages9
JournalJournal of Investigative Dermatology
Volume131
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Receptor, Fibroblast Growth Factor, Type 2
MicroRNAs
Keratinocytes
Psoriasis
Down-Regulation
Skin
Untranslated RNA
Differentiation Antigens
Cell proliferation
Gene Expression Regulation
Luciferases
Gene expression
Small Interfering RNA

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

MiR-125b, a MicroRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. / Xu, Ning; Brodin, Petter; Wei, Tianling; Meisgen, Florian; Eidsmo, Liv; Nagy, N.; Kemény, L.; Ståhle, Mona; Sonkoly, Enikö; Pivarcsi, Andor.

In: Journal of Investigative Dermatology, Vol. 131, No. 7, 07.2011, p. 1521-1529.

Research output: Contribution to journalArticle

Xu, Ning ; Brodin, Petter ; Wei, Tianling ; Meisgen, Florian ; Eidsmo, Liv ; Nagy, N. ; Kemény, L. ; Ståhle, Mona ; Sonkoly, Enikö ; Pivarcsi, Andor. / MiR-125b, a MicroRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 7. pp. 1521-1529.
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