Plasma microRNA profiling predicts HIV-associated neurocognitive disorder
OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a common neurological disorder among HIV-infected patients despite the availability of combination antiretroviral therapy. Host-encoded microRNAs (miRNA) regulate both host and viral gene expression contributing to HAND pathogenesis and can also serve as disease biomarkers. Herein, plasma miRNA profiles were investigated in HIV/AIDS patients with HAND.
METHODS: Discovery and Validation Cohorts comprising HIV/AIDS patients were studied that included patients with and without HAND (non-HAND). Plasma miRNA levels were measured by array hybridization and verified by quantitative real-time reverse transcriptase PCR (qRT-PCR). Multiple bioinformatic and biostatistical analyses were applied to the data from each cohort.
RESULTS: Expression analyses identified nine miRNAs in the Discovery Cohort (HAND, n = 22; non-HAND, n = 25) with increased levels (≥two-fold) in the HAND group compared with the non-HAND group (P < 0.05). In the Validation Cohort (HAND, n = 12; non-HAND, n = 12) upregulation (≥two-fold) of three miRNAs (miR-3665, miR-4516 and miR-4707-5p) was observed in the HAND group that were also increased in the Discovery Cohort's HAND patients, which were verified subsequently by qRT-PCR. Receiver-operating characteristic curve analyses for the three miRNAs also pointed to the diagnosis of HAND (area under curve, 0.87, P < 0.005). Bioinformatics tools predicted that all three miRNAs targeted sequences of genes implicated in neural development, cell death, inflammation, cell signalling and cytokine functions.
CONCLUSION: Differentially expressed plasma-derived miRNAs were detected in HIV/AIDS patients with HAND that were conserved across different patient cohorts and laboratory methods. Plasma-derived miRNAs might represent biomarkers for HAND and also provide insights into disease mechanisms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
AIDS (London, England) - 30(2016), 13 vom: 24. Aug., Seite 2021-31 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Asahchop, Eugene L [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 18.12.2017 Date Revised 22.05.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000001160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM260465895 |
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| 245 | 1 | 0 | |a Plasma microRNA profiling predicts HIV-associated neurocognitive disorder |
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| 500 | |a Date Completed 18.12.2017 | ||
| 500 | |a Date Revised 22.05.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a common neurological disorder among HIV-infected patients despite the availability of combination antiretroviral therapy. Host-encoded microRNAs (miRNA) regulate both host and viral gene expression contributing to HAND pathogenesis and can also serve as disease biomarkers. Herein, plasma miRNA profiles were investigated in HIV/AIDS patients with HAND | ||
| 520 | |a METHODS: Discovery and Validation Cohorts comprising HIV/AIDS patients were studied that included patients with and without HAND (non-HAND). Plasma miRNA levels were measured by array hybridization and verified by quantitative real-time reverse transcriptase PCR (qRT-PCR). Multiple bioinformatic and biostatistical analyses were applied to the data from each cohort | ||
| 520 | |a RESULTS: Expression analyses identified nine miRNAs in the Discovery Cohort (HAND, n = 22; non-HAND, n = 25) with increased levels (≥two-fold) in the HAND group compared with the non-HAND group (P < 0.05). In the Validation Cohort (HAND, n = 12; non-HAND, n = 12) upregulation (≥two-fold) of three miRNAs (miR-3665, miR-4516 and miR-4707-5p) was observed in the HAND group that were also increased in the Discovery Cohort's HAND patients, which were verified subsequently by qRT-PCR. Receiver-operating characteristic curve analyses for the three miRNAs also pointed to the diagnosis of HAND (area under curve, 0.87, P < 0.005). Bioinformatics tools predicted that all three miRNAs targeted sequences of genes implicated in neural development, cell death, inflammation, cell signalling and cytokine functions | ||
| 520 | |a CONCLUSION: Differentially expressed plasma-derived miRNAs were detected in HIV/AIDS patients with HAND that were conserved across different patient cohorts and laboratory methods. Plasma-derived miRNAs might represent biomarkers for HAND and also provide insights into disease mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 700 | 1 | |a Akinwumi, Segun M |e verfasserin |4 aut | |
| 700 | 1 | |a Branton, William G |e verfasserin |4 aut | |
| 700 | 1 | |a Fujiwara, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, M John |e verfasserin |4 aut | |
| 700 | 1 | |a Power, Christopher |e verfasserin |4 aut | |
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