title: Comprehensive analysis of alterations in the miRNome in response to photodynamic treatment.
abstract: Photodynamic therapy (PDT) is a local tumour treatment accepted for a number of indications. PDT operates via the cellular stress response through the production of reactive oxygen species and subsequent cellular damage, resulting in cell death. Although PDT-induced signalling and cytotoxicity mechanisms have been investigated, the effect of PDT on microRNA (miRNA) expression is largely unknown. Therefore, we conducted a comprehensive microarray-based analysis of the miRNome of human epidermoid carcinoma cells (A431) following in vitro photodynamic treatment using polyvinylpyrrolidone hypericin (PVPH) as a photosensitiser and nearly homogeneous apoptosis-inducing conditions. Using microarray analysis we found eight miRNAs to be significantly differentially expressed 5h post treatment compared with the baseline levels and three miRNAs with more than 2-fold differential expression that could be detected in 1 or 2 biological replicates. The verification of these results by quantitative RT-PCR including a detailed time-course revealed an up to 15-fold transient over-expression of miR-634, miR-1246, miR-1290 and miR-487b compared with the basal level. For these miRNAs, in silico mRNA target prediction yielded numerous target transcripts involved in the regulation of cell stress, apoptosis, cell adherence and proliferation. This study provides the first comprehensive miRNome analysis after PDT treatment and may help to develop novel miRNA-based therapeutic approaches to further increase the efficiency of PDT.
authors: Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria. d.bach@salk.at
authors: Doris
authors: D
authors: Bach
authors: Julia
authors: J
authors: Fuereder
authors: Michael
authors: M
authors: Karbiener
authors: Marcel
authors: M
authors: Scheideler
authors: Anna Lena
authors: AL
authors: Ress
authors: Daniel
authors: D
authors: Neureiter
authors: Ralf
authors: R
authors: Kemmerling
authors: Otto
authors: O
authors: Dietze
authors: Markus
authors: M
authors: Wiederstein
authors: Frieder
authors: F
authors: Berr
authors: Kristjan
authors: K
authors: Plaetzer
authors: Tobias
authors: T
authors: Kiesslich
authors: Martin
authors: M
authors: Pichler
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011205:Povidone / Q000494:pharmacology; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects* / Q000528:radiation effects*
chemical_list: D035683:MicroRNAs; D017319:Photosensitizing Agents; D011205:Povidone