Integrated Analysis of the miRNA-mRNA Regulatory Network Involved in HIV-Associated Neurocognitive Disorder

Abstract

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND have not yet been completely revealed. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulate these genes are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the progression of HAND, and our findings provide potential therapeutic targets and clues of HAND.

Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway

“…microRNAs (miRNAs), which belong to a class of short endogenous non-coding RNA, are enabled to govern gene expression, especially at the post-transcriptional level via targeting the 3' UTR of messenger RNA (mRNA) [ 39 ]. Multiple miRNAs are shown to modulate cell development and function, which mainly inhibit the expressions of Foxp3 and other related genes via binding to mRNA 3′UTR.…”

The involvement of microRNAs in HCV and HIV infection

“… 37 , 39 Multiple studies demonstrated how the dysregulation of miR-7-3p, miRNAs-30, miRNA-125b, miRNA-150, miR-186, miR-210, and miR-222 has a negative impact on viral infection. 40 – 43 These miRNAs were found to target genes of Dicer, NTNG1, EFNB2, CXCL12, or HRB (HIV-1 Rev-binding protein), and HIV-EP2 (HIV-1 enhancer-binding protein 2). 40 , 42 The downregulation of these genes eventually leads to reduce viral expression.…”

“… 40 , 42 The downregulation of these genes eventually leads to reduce viral expression. 40 – 42 Few other microRNAs exhibiting antiviral activities are listed here ( Table 1 ). 25 – 27 , 29 , 31 , 35 , 38 , 44 – 51 …”

“…37,39 Multiple studies demonstrated how the dysregulation of miR-7-3p, miRNAs-30, miRNA-125b, miRNA-150, miR-186, miR-210, and miR-222 has a negative impact on viral infection. [40][41][42][43] 48 Targets a Tat cofactor, Cyclin-T1 Inhibits HIV-1 via repression of cyclin-T1 miR-191-5p 49 Targets and inhibits expression of CCR1 and NUP50 Inhibits viral replication via target repression. miR-28 29,50 miR-125b 29,50 miR-150 29,50 miR-223 29,50 miR-382-5p 29,50 Target the 3′ UTR of HIV-1 mRNA Decreases CD4 + T-cell activation vmiRNAs vmiR88 51 vmiR99 51 Mediates TNF-α release Facilitates immune activation miR-H1 25 Targets AATF, c-Myc and Dicer Promotes HIV replication miR-TAR 26,27 Targets AGO proteins, Caspase 8, Aiolos, and NPM/ B23…”

“…40,42 The downregulation of these genes eventually leads to reduce viral expression. [40][41][42] Few other microRNAs exhibiting antiviral activities are listed here (Table 1). [25][26][27]29,31,35,38,[44][45][46][47][48][49][50][51] In addition, there are some other miRNAs, which show antiviral properties by sharing a common target that is Purine-rich element-binding protein…”