HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300

Feng Zhou, Xiaomei Liu, Dongjiao Zuo, Min Xue, Lin Gao, Ying Yang, Jing Wang, Liping Niu, Qianwen Cao, Xiangyang Li, Hui Hua, Bo Zhang, Minmin Hu, Dianshuai Gao, Kuiyang Zheng, Yoshihiro Izumiya, Renxian Tang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: HIV-associated neurocognitive disorder (HAND) is a neurodegenerative disease associated with persistent neuroinflammation and subsequent neuron damage. Pro-inflammatory factors and neurotoxins from activated astrocytes by HIV-1 itself and its encoded proteins, including the negative factor (Nef), are involved in the pathogenesis of HAND. This study was designed to find potential lncRNAs that regulate astrocyte functions and inflammation process. Methods: We performed microarray analysis of lncRNAs from primary mouse astrocytes treated with Nef protein. Top ten lncRNAs were validated through real-time PCR analysis. Gene ontology (GO) and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. RIP and ChIP assays were performed to demonstrate the mechanism of lncRNA regulating gene expression. Results: There were 638 co-upregulated lncRNAs and 372 co-downregulated lncRNAs in primary astrocytes treated with Nef protein for both 6 h and 12 h. GO and KEGG pathway analysis showed that the biological functions of top differential-expressed mRNAs were associated with inflammatory cytokines and chemokine. Knockdown of lncRNA AK006025, not AK138360, inhibited significantly CXCL9, CXCL10 (IP-10), and CXCL11 expression in astrocytes treated with Nef protein. Mechanism study showed that AK006025 associated with CBP/P300 was enriched in the promoter of CXCL9, CXCL10, and CXCL11 genes. Conclusions: Our findings uncovered the expression profiles of lncRNAs and mRNAs in vitro, which might help to understand the pathways that regulate astrocyte activation during the process of HAND.

Original languageEnglish (US)
Article number303
JournalJournal of Neuroinflammation
Volume15
Issue number1
DOIs
StatePublished - Oct 31 2018

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Keywords

  • Astrocytes
  • CBP/P300
  • HIV-1
  • HIV-associated neurocognitive disorder
  • Inflammation
  • lncRNAs
  • Nef

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Zhou, F., Liu, X., Zuo, D., Xue, M., Gao, L., Yang, Y., Wang, J., Niu, L., Cao, Q., Li, X., Hua, H., Zhang, B., Hu, M., Gao, D., Zheng, K., Izumiya, Y., & Tang, R. (2018). HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300. Journal of Neuroinflammation, 15(1), [303]. https://doi.org/10.1186/s12974-018-1343-x