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ORIGINAL RESEARCH article
Front. RNA Res.
Sec. Non-coding RNA
Volume 3 - 2025 | doi: 10.3389/frnar.2025.1566829
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Dengue virus (DENV) is a zoonotic disease transmitted to humans via mosquito bites. Viral infection is systemic in humans and can lead to organ failure including in the liver. Since there are many molecular changes that precede liver failure, identification of progress at the molecular level is informative. As an RNA virus, DENV perturbs non-coding RNAs including microRNAs. Here we examine microRNA profiles in hepatoma cells using small molecule-mediated annotation of miRNA targets. It was previously shown that treatment with the broadly antiviral oxysterol 25-hydroxycholesterol (25HC) induces the expression of antiviral microRNAs in the liver. Herein, we show that 25HC is potently antiviral against Dengue virus and identify miR-4488 as a microRNA which is overexpressed during infection and downregulated with oxysterol treatment. We also show that miR-4488 is downregulated when the viral levels are lowered using siRNA, suggesting that this microRNA is involved in the host-response to infection. Since miR-4488 levels closely correlate with DENV levels in the liver, it serves as a biomarker for virus infection in the liver and may contribute the overall effects of DENV in the liver.
Keywords: microRNA, Dengue (DENV), NanoString, 25-hydroxy cholesterol, miR-4488
Received: 25 Jan 2025; Accepted: 02 Apr 2025.
Copyright: © 2025 Pezacki, Filip, Alonzi, Ahmed, Ahmed, Evers, Uguccioni and Pezacki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
John Paul Pezacki, University of Ottawa, Ottawa, Canada
John Paul Pezacki, University of Ottawa, Ottawa, Canada
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