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Citation: Cell Death and Disease (2016) 7, e2108; doi:ten.1038/cddis.2016.29 2016 Macmillan Publishers Limited All rights reserved 2041-4889/www.nature.com/cddisThe miR-27a-calreticulin axis affects drug-induced immunogenic cell death in human colorectal cancer cellsT Colangelo1, G Polcaro1, P Ziccardi1, L Muccillo1, M Galgani2, B Pucci3, M Rita Milone3, A Budillon3, M Santopaolo4, G Mazzoccoli5, G Matarese2,4, L Sabatino1 and V Colantuoni*,Immunogenic cell death (ICD) evoked by chemotherapeutic agents implies emission of selected damage-associated molecular patterns (DAMP) including cell surface exposure of calreticulin, secretion of ATP and HMGB1. We sought to confirm no matter whether miR-27a is implicated in ICD, possessing demonstrated that it directly targets calreticulin. To this purpose, we exposed colorectal cancer cell lines, genetically modified to express high or low miR-27a levels, to two bona fide ICD inducers (mitoxantrone and oxaliplatin). Low miR-27a-expressing cells displayed additional ecto-calreticulin around the cell surface and elevated ATP and HMGB1 secretion than high miR-27a-expressing ones in time-course experiments upon drug exposure. A calreticulin target protector counteracted the miR-27a effects although certain siRNAs mimicked them, confirming the outcomes reported.DNASE1L3 Protein Formulation Furthermore, miR-27a negatively influenced the PERK-mediated route as well as the late PI3K-dependent secretory step with the unfolded protein response to endoplasmic reticulum stress, suggesting that miR-27a modulates the complete ICD system.IFN-beta Protein medchemexpress Interestingly, upon chemotherapeutic exposure, low miR-27a levels linked with an earlier and stronger induction of apoptosis and with morphological and molecular options of autophagy.PMID:32180353 Remarkably, in ex vivo setting, under exactly the same chemotherapeutic induction, the conditioned media from high miR-27aexpressing cells impeded dendritic cell maturation though elevated the secretion of distinct cytokines (interleukin (IL)-4, IL-6, IL-8) and negatively influenced CD4+ T-cell interferon production and proliferation, all markers of a tumor immunoevasion approach. In conclusion, we provide the initial proof that miR-27a impairs the cell response to drug-induced ICD by way of the regula.
