ef70c6dde66e4503fbd84639f373412c pmc_10487266.pdf e0ef9b3064b7def51c02961edc235e4a5b5a362c pmc_10487266.pdf fab8fa9dc9c875695ef87f08a9edb5b8a35302488233c33795225466bf157c2d pmc_10487266.pdf Title: Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy Subject: Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles. In this study, 18 DM, 12 IMNM, 6 AS, 6 IBM, and 6 histologically normal muscle biopsies underwent miRNA profiling using the NanoString nCounter system. Eleven miRNAs were exclusively differentially expressed in DM compared to controls, seven miRNAs were only differentially expressed in AS, and nine miRNAs were specifically upregulated in IBM. No differentially expressed miRNAs were identified in IMNM. We also analyzed miRNA-mRNA associations to identify putative targets of differentially expressed miRNAs. In DM and AS, these were predominantly related to inflammation and cell cycle progression. Moreover, our analysis showed an association between miR-30a-3p, miR-30e-3p, and miR-199b-5p downregulation in DM and the upregulation of target genes induced by type I interferon. In conclusion, we show that muscle biopsies from DM, AS, and IBM patients have unique miRNA signatures and that these miRNAs might play a role in regulating the expression of genes known to be involved in IIM pathogenesis. Keywords: inflammatory myopathies; myositis; miRNA; NanoString; nCounter Author: Sandra Muñoz-Braceras, Iago Pinal-Fernandez, Maria Casal-Dominguez, Katherine Pak, José César Milisenda, Shajia Lu, Massimo Gadina, Faiza Naz, Gustavo Gutierrez-Cruz, Stefania Dell’Orso, Jiram Torres-Ruiz, Josep Maria Grau-Junyent, Albert Selva-O’Callaghan, Julie J. Paik, Jemima Albayda, Lisa Christopher-Stine, Thomas E. Lloyd, Andrea M. Corse and Andrew L. Mammen Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Sep 2 11:56:09 2023 CEST ModDate: Sat Sep 2 12:08:30 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1667703 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 HIHUZY+VnURWPalladioL Type 1 Custom yes yes no 15 0 IHPEWP+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 CZIDWD+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 KAIDOB+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 ALJFJM+Calibri CID TrueType Identity-H yes yes yes 87 0 ALJDJA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 93 0 ALJDJB+PalatinoLinotype CID TrueType Identity-H yes yes yes 96 0 ALJDJC+PalatinoLinotype TrueType WinAnsi yes yes no 102 0 ALJDJE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 105 0 ALJEGC+PalatinoLinotype TrueType MacRoman yes yes no 108 0 ALJDJA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 ALJDJB+PalatinoLinotype CID TrueType Identity-H yes yes yes 130 0 ALJDJC+PalatinoLinotype TrueType WinAnsi yes yes no 136 0 ALJDJD+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 139 0 ALJDJE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 145 0 ALJEGC+PalatinoLinotype TrueType MacRoman yes yes no 148 0 SOSCBV+CMSY10 Type 1 Builtin yes yes no 155 0 ALJHFD+Arial CID TrueType Identity-H yes yes yes 175 0 ALJDJA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 181 0 ALJDJB+PalatinoLinotype CID TrueType Identity-H yes yes yes 184 0 ALJDJC+PalatinoLinotype TrueType WinAnsi yes yes no 190 0 ALJDJD+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 193 0 ALJDJE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 199 0 ALJEGC+PalatinoLinotype TrueType MacRoman yes yes no 202 0 ALJHFD+Arial CID TrueType Identity-H yes yes yes 221 0 ALJDJA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 227 0 ALJDJB+PalatinoLinotype CID TrueType Identity-H yes yes yes 230 0 ALJDJC+PalatinoLinotype TrueType WinAnsi yes yes no 236 0 ALJDJE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 239 0 ALJEGC+PalatinoLinotype TrueType MacRoman yes yes no 242 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-02-02 02:33:04 CET RepresentationInformation: pmc_10487266.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-10-02 02:27:10 CEST Size: 1667703 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 463 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Subjects and Sample Preparation Destination: subsection.2.1 Item: Title: NanoString miRNA Assay and Analysis of nCounter Data Destination: subsection.2.2 Item: Title: Library Preparation and Analysis of mRNA Sequencing Data Destination: subsection.2.3 Item: Title: Analysis of miRNA mRNA Associations Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Unique miRNA Profiles in Each Type of IIM Destination: subsection.3.1 Item: Title: Correlation Analyses Suggest There Is a Coordinated Expression of Deregulated miRNAs and Regulation of Differentially Expressed Targets Destination: subsection.3.2 Item: Title: The Abundance of Differentially Expressed miRNAs and the Expression of Relevant Genes in Myositis Are Associated Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.A. Info: Title: Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy Author: Sandra Muñoz-Braceras, Iago Pinal-Fernandez, Maria Casal-Dominguez, Katherine Pak, José César Milisenda, Shajia Lu, Massimo Gadina, Faiza Naz, Gustavo Gutierrez-Cruz, Stefania Dell’Orso, Jiram Torres-Ruiz, Josep Maria Grau-Junyent, Albert Selva-O’Callaghan, Julie J. Paik, Jemima Albayda, Lisa Christopher-Stine, Thomas E. Lloyd, Andrea M. Corse and Andrew L. Mammen Subject: Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles. In this study, 18 DM, 12 IMNM, 6 AS, 6 IBM, and 6 histologically normal muscle biopsies underwent miRNA profiling using the NanoString nCounter system. Eleven miRNAs were exclusively differentially expressed in DM compared to controls, seven miRNAs were only differentially expressed in AS, and nine miRNAs were specifically upregulated in IBM. No differentially expressed miRNAs were identified in IMNM. We also analyzed miRNA-mRNA associations to identify putative targets of differentially expressed miRNAs. In DM and AS, these were predominantly related to inflammation and cell cycle progression. Moreover, our analysis showed an association between miR-30a-3p, miR-30e-3p, and miR-199b-5p downregulation in DM and the upregulation of target genes induced by type I interferon. In conclusion, we show that muscle biopsies from DM, AS, and IBM patients have unique miRNA signatures and that these miRNAs might play a role in regulating the expression of genes known to be involved in IIM pathogenesis. 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