Large-scale screening of circulating microRNAs in individuals with HIV-1 mono-infections reveals specific liver damage signatures

被引:8
作者
Franco, Sandra [1 ]
Buccione, Daniela [2 ]
Pluvinet, Raquel [3 ]
Mothe, Beatriz [1 ]
Ruiz, Lidia [1 ]
Nevot, Maria [1 ]
Jordan-Paiz, Ana [1 ]
Ramos, Laia [3 ]
Ausso, Susanna [3 ]
Morillas, Rosa M. [4 ]
Sumoy, Lauro [3 ]
Angel Martinez, Miguel [1 ]
Tural, Cristina [2 ]
机构
[1] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, IrsiCaira, Badalona, Spain
[2] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Internal Med Dept, Badalona, Spain
[3] IGTP, High Content Genom & Bioinformat Unit, Can Ruti Campus, Badalona, Spain
[4] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Liver Unit, CIBERehd, Badalona, Spain
关键词
HIV-1; infection; Circulating microRNAs; Liver disease; HEPATOCELLULAR-CARCINOMA; MIRNA PROFILE; EXPRESSION; TARGETS; CANCER; IDENTIFICATION; PROLIFERATION; FIBROSIS; SEQUENCE; PLASMA;
D O I
10.1016/j.antiviral.2018.05.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Human immunodeficiency virus type 1 (HIV-1)-induced inflammation and/or long-term antiretroviral drug toxicity may contribute to the evolution of liver disease. We investigated circulating plasma microRNAs (miRNAs) as potential biomarkers of liver injury in patients mono-infected with HIV-1. We performed large-scale deep sequencing analyses of small RNA level on plasma samples from patients with HIV-1 mono-infection that had elevated or normal levels of alanine aminotransferase (ALT) or focal nodular hyperplasia (FNH). Hepatitis C virus (HCV) mono-infected patients were also studied. Compared to healthy donors, patients with HIV-1 or HCV mono-infections showed significantly altered (fold change > 2, adjusted p < 0.05) level of 25 and 70 miRNAs, respectively. Of the 25 altered miRNAs found in patients with HIV-1, 19 were also found in patients mono infected with HCV. Moreover, 13 of the 14 most up-regulated miRNAs (range: 9.3-3.4-fold increase) in patients with HCV mono-infections were also up-regulated in patients with HIV-1 mono-infections. Importantly, most of these miRNAs significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels, and liver fibrosis stage (p < 0.05). MiR-122-3p and miR-193b-5p were highly up-regulated HIV-1 mono-infected patients with elevated ALT or FNH, but not in HIV-1 patients with normal levels of ALT. These results reveal that HIV-1 infections impacted liver-related miRNA levels in the absence of an HCVco-infection, which highlights the potential of miRNAs as biomarkers for the progression of liver injury in HIV-1 infected patients.
引用
收藏
页码:106 / 114
页数:9
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