title: Artificial Analogues of Circulating Box C/D RNAs Induce Strong Innate Immune Response and MicroRNA Activation in Human Adenocarcinoma Cells.
abstract: Fragments of small nucleolar RNAs (snoRNAs) were found among various non-coding RNAs (ncRNAs) circulating in human blood. Currently, the function of such cell-free sno-derived-RNAs is not clearly defined. This work is aimed at identifying regulatory pathways controlled by extracellular snoRNAs. In order to determine the molecular targets and pathways affected by artificial snoRNAs, we performed Illumina array analysis of MCF-7 human adenocarcinoma cells transfected with box C/D RNAs. The genes related to the innate immune response and apoptotic cascades were found to be activated in transfected cells compared with control cells. Intriguingly, the transfection of MCF-7 cells with artificial box C/D snoRNAs also increased the transcription of several microRNAs, such as mir-574, mir-599 and mir-21. Our data demonstrated that extracellular snoRNAs introduced into human cells may function as gene expression modulators, with activation of microRNA genes being one of the regulatory mechanisms.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia. stepanovga@niboch.nsc.ru.
authors.forename: Grigory A
authors.initials: GA
authors.lastname: Stepanov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Filippova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Nushtaeva
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kuligina
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Koval
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Richter
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB of RAS, Lavrentiev ave. 8, Novosibirsk, 630090, Russia. semenov@niboch.nsc.ru.
authors.forename: Dmitriy V
authors.initials: DV
authors.lastname: Semenov
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D020537:RNA, Small Nucleolar / Q000097:blood / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C524940:MIRN21 microRNA, human; C558811:MIRN574 microRNA, human; C000608803:MIRN599 microRNA, human; D035683:MicroRNAs; D020537:RNA, Small Nucleolar
keywords: Circulating RNAs; Innate immune response; MicroRNAs; Small nucleolar RNAs