Interestingly, most of them correlated positively although miRNAs were downregulated. Among them, hsa miR 137, selleck compound hsa miR 153, hsa miR 299 5p, hsa miR 218 and hsa miR 376a were outstanding due to their functional correlation with numerous genes. It is interesting to see that most of the miRNA are down regulated in HAD versus HIV non demented brains, and positively correlated with their mRNA target, which is supported by previous findings. To validate this correlation further, miRNA mimic of miR 137 and negative control treatments were carried out. That led a significant decrease in expression levels of NUFIB1, SLC, RNF, BAG4, SPRED, ZRANB at 24 h after transfection, which are all the genes negatively regulated by miR137 according to the correl ation network we found.

This result added extra confi dence to our correlation network. Discussion This is the first joint study of whole genome mRNA and miRNA profiling using individual human brain RNA from autopsies of HAD and HIV non dementia patients. In this study, we initially compared mRNA and miRNA data at the clustering, gene ontology, and pathway levels. Following that, SA BNs correlating miRNAs and mRNAs by their expression levels were performed to validate the accurate prediction of genes potentially tar geted by dysregulated miRNAs. The clustering and gene ontology results showed ex cellent functional concordance between mRNA and miRNA, demonstrating the significant involvement of neuronal cellular components and biological processes such as, signal transduction, transcriptional regulation, metabolism, response to stimuli, cell cycle apoptosis, protein modification, neuronal processes and ion trans port, respectively.

This intrinsic functional consistency between miRNA and mRNA has given an extra power to our findings in relation to understanding the genomic basis of HIV neuropathogenesis and HIV mediated neurodegeneration. Moreover, the DE miRNAs were more robust than their mRNA counterparts in providing a comprehensive snapshot of cellular components and biological processes involved in neuropathology and neurodegeneration. Compared to DE miRNAs, DE mRNAs could only predict elemental functional path ways and processes related to neuropathology. DE miR NAs revealed the participation of additional cellular components and biological processes, which also concurs with biological processes of mRNA.

Interestingly, these findings are consistent with study, which has been done using CSF of HIVE patients. The most plausible ex planation for the comprehensiveness of miRNA coverage as compared to their mRNA counterpart is that a single miRNA or the miRNAs belonging to the same family in the cluster can target several hundred genes within a bio logical process Dacomitinib or pathway. Therefore, it is not surprising that miRNA gives broader information compared to mRNA.