title: Role of microRNA profile modifications in hepatitis C virus-related mixed cryoglobulinemia.
abstract: Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin's lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders.
authors: Center for Systemic Manifestations of Hepatitis Viruses, MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Elisa
authors: E
authors: Fognani
authors: Carlo
authors: C
authors: Giannini
authors: Alessia
authors: A
authors: Piluso
authors: Laura
authors: L
authors: Gragnani
authors: Monica
authors: M
authors: Monti
authors: Patrizio
authors: P
authors: Caini
authors: Jessica
authors: J
authors: Ranieri
authors: Teresa
authors: T
authors: Urraro
authors: Elisa
authors: E
authors: Triboli
authors: Giacomo
authors: G
authors: Laffi
authors: Anna Linda
authors: AL
authors: Zignego
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003449:Cryoglobulinemia / Q000097:blood* / Q000235:genetics / Q000821:virology; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000235:genetics / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; C528163:MIRN26 microRNA, human
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