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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1558842
This article is part of the Research TopicHIV-1 Tat, An Enhancer of Virus Infectivity and Disease Promoter: Target for Preventive and Therapeutic InterventionsView all 5 articles
Role of lncRNA Xist-miR-124-CCL2 axis in HIV Tat-mediated microglial activation and neuroinflammation
Provisionally accepted- University of Nebraska Medical Center, Omaha, United States
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HIV proteins, such as the Transactivator of transcription (Tat), have been shown to mediate neuroinflammation in the central nervous system, by triggering the release of pro-inflammatory cytokines and chemokines. Long noncoding RNAs (lncRNAs) play a crucial role in regulating gene expression by sponging competitive endogenous microRNAs (miRs), in turn, influencing the expression of downstream target genes. While several mRNAs have been implicated in HIV Tat mediated microglia activation, the role of lncRNAs in this process is not well examined. The current study was aimed at assessing the role of lncRNA Xist-miR-124-CCL2 axis in HIV Tatexposed microglial cells. Our findings suggest that HIV Tat upregulated the expression of lncRNA Xist while also downregulating the expression of miR-124 in mouse primary microglial cells. In silico analyses identified miR-124 as a novel binding partner of both lncRNA Xist as well as the 3′-UTR of CCL2. Both gene silencing of lncRNA Xist as well as overexpression of miR-124 approaches highlighted the role of the lncRNA Xist-miR-124-CCL2 axis in HIV Tat-mediated activation of mouse primary microglial cells. The interaction between lncRNA Xist and miR-124 was confirmed using the dual luciferase reporter and Argonaute immunoprecipitation assays. In vivo validation using doxycycline-inducible HIV Tat transgenic mice further validated the in vitro findings. Overall, these results indicated that HIV Tat upregulated the expression of lncRNA Xist, which, in turn, sponged miR-124, ultimately leading to increased CCL2 expression and subsequent microglial activation.
Keywords: CCL2, HIV Tat, lncRNA XIST, Microglia, mir-124, Neuroinflammation
Received: 11 Jan 2025; Accepted: 11 Apr 2025.
Copyright: © 2025 Periyasamy, Singh, Oladapo, Kannan and Buch. 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: Palsamy Periyasamy, University of Nebraska Medical Center, Omaha, United States
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