HCV chronic infection is closely related to the development of lymphoproliferative disorders (LPDs), mainly mixed cryoglobulinemia (MC) and some types of lymphoma. The pathogenesis of HCV-LPDs is still largely unknown. Modification of the expression levels of specific microRNAs (miRNAs) has been associated with different autoimmune and/or LPDs. Scarce data exist about the modifications in miRNA expression levels in HCV-related 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 levels of miR-Let7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 were evaluated by Real Time PCR in 167 HCV patients (75 with MC [HCV-MC], 11 with HCV-related NHL [HCV-NHL], 81 without LPD [HCV]) and in 35 healthy blood donors (HS). Synthetic C. Elegans miR-39 was added as external control. Similar expression levels for miR-146a were observed in all studied groups. A significant increase of miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression levels was detected in PBMCs from only NHL patients whereas a significant decrease of 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 PBMC 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. Results obtained for miR-21, miR-16 and miR-155 are consistent with the upregulation previously observed in other lymphatic malignancies. 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
microRNA PROFILE MODIFICATIONS IN HEPATITIS C VIRUS-RELATED MIXED CRYOGLOBULINEMIA / Elisa Fognani; Alessia Piluso; Laura Gragnani; Carlo Giannini; Patrizio Caini; Monica Monti; Jessica Ranieri; Teresa Urraro; Elisa Triboli; Giacomo Laffi; Anna Linda Zignego. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - STAMPA. - 58:(2013), pp. 185-186.
microRNA PROFILE MODIFICATIONS IN HEPATITIS C VIRUS-RELATED MIXED CRYOGLOBULINEMIA
FOGNANI, ELISA;PILUSO, ALESSIA;GRAGNANI, LAURA;MONTI, MONICA;RANIERI, JESSICA;URRARO, TERESA;LAFFI, GIACOMO;ZIGNEGO, ANNA LINDA
2013
Abstract
HCV chronic infection is closely related to the development of lymphoproliferative disorders (LPDs), mainly mixed cryoglobulinemia (MC) and some types of lymphoma. The pathogenesis of HCV-LPDs is still largely unknown. Modification of the expression levels of specific microRNAs (miRNAs) has been associated with different autoimmune and/or LPDs. Scarce data exist about the modifications in miRNA expression levels in HCV-related 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 levels of miR-Let7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 were evaluated by Real Time PCR in 167 HCV patients (75 with MC [HCV-MC], 11 with HCV-related NHL [HCV-NHL], 81 without LPD [HCV]) and in 35 healthy blood donors (HS). Synthetic C. Elegans miR-39 was added as external control. Similar expression levels for miR-146a were observed in all studied groups. A significant increase of miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression levels was detected in PBMCs from only NHL patients whereas a significant decrease of 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 PBMC 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. Results obtained for miR-21, miR-16 and miR-155 are consistent with the upregulation previously observed in other lymphatic malignancies. 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
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