title: microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.
abstract: Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Nathalie
authors: N
authors: Arts
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Stefania
authors: S
authors: Cané
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Marc
authors: M
authors: Hennequart
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Juliette
authors: J
authors: Lamy
authors: de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors: Guido
authors: G
authors: Bommer
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Benoît
authors: B
authors: Van den Eynde
authors: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.
authors: Etienne
authors: E
authors: De Plaen
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor