title: UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes.
abstract: MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.
authors.affiliation: Institute of Radiation Biology, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kraemer
authors.affiliation: Department Molecular Cell Biology, Center of Dermatology, Elbekliniken Stade/Buxtehude, Buxtehude, Germany.
authors.forename: I-Peng
authors.initials: IP
authors.lastname: Chen
authors.affiliation: Department Molecular Cell Biology, Center of Dermatology, Elbekliniken Stade/Buxtehude, Buxtehude, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Henning
authors.affiliation: Department Molecular Cell Biology, Center of Dermatology, Elbekliniken Stade/Buxtehude, Buxtehude, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Faust
authors.affiliation: Department Molecular Cell Biology, Center of Dermatology, Elbekliniken Stade/Buxtehude, Buxtehude, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Volkmer
authors.affiliation: Institute of Radiation Biology, Helmholtz Center Munich, Neuherberg, Germany ; Radiation Biology, Technical University of Munich, München, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: Institute of Radiation Biology, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Moertl
authors.affiliation: Department Molecular Cell Biology, Center of Dermatology, Elbekliniken Stade/Buxtehude, Buxtehude, Germany.
authors.forename: Ruediger
authors.initials: R
authors.lastname: Greinert
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D003198:Computer Simulation; D015870:Gene Expression / Q000528:radiation effects; D053263:Gene Regulatory Networks / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D015398:Signal Transduction / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C552430:MIRN23a microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C087360:RRAS2 protein, human; D020559:Monomeric GTP-Binding Proteins