Center for Systemic Manifestations of Hepatitis Viruses, MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
PLoS One. 2013 May 1;8(5):e62965. doi: 10.1371/journal.pone.0062965. Print 2013.
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.
丙型肝炎病毒感染与淋巴增生性疾病（LPD）密切相关，包括混合性冷球蛋白血症（MC）和某些淋巴瘤。特定 microRNA（miRNA）表达的改变与不同的自身免疫性疾病和/或 LPD 有关。关于丙型肝炎病毒相关 LPD 中 miRNA 表达的改变尚无数据。本研究旨在分析一组先前与自身免疫性/LPD 相关的 miRNA 在大量丙型肝炎病毒患者中的表达水平，这些患者有或没有 MC 或非霍奇金淋巴瘤（NHL），以确定丙型肝炎病毒感染演变的潜在标志物。通过实时 PCR 评估了 167 例丙型肝炎病毒患者（75 例有 MC [MC-HCV]，11 例有丙型肝炎病毒相关 NHL [NHL-HCV]，81 例无 LPD [HCV]）和 35 例健康对照者（HS）的 PBMC 中 miR-Let-7d、miR-16、miR-21、miR-26b、miR-146a 和 miR-155 的表达。仅在 NHL 患者的 PBMC 中检测到 miR-21（p<0.001）、miR-16（p<0.01）和 miR-155（p<0.01）表达显著增加，而在 MC 和 NHL 患者中均检测到 miR-26b 显著降低（p<0.01）与 HS 和 HCV 组相比。在接受抗病毒治疗后完全病毒学和临床应答的 35 例 HCV-MC 患者的治疗后 PBMC 中观察到 miR-26b 水平的恢复。这项研究首次表明，发生 MC 和/或 NHL 的丙型肝炎病毒患者 PBMC 中的特定 microRNA 受到不同的调节。miR-26b 的特异性、可逆下调强烈表明其在丙型肝炎病毒相关 LPD 发病机制中的关键作用及其作为这些疾病丙型肝炎病毒感染演变的生物标志物的有用性。
