NF-кB-regulated micro RNAs (miRNAs) in primary human brain cells

Abstract

Micro RNAs (miRNAs), small and labile ~22 nucleotide-sized fragments of single stranded RNA, are important regulators of messenger (mRNA) complexity and in shaping the transcriptome of a cell. In this communication, we utilized amyloid beta 42 (Aβ42) peptides and interleukin-1beta (IL-1β) as a combinatorial, physiologically-relevant stress to induce miRNAs in human primary neural (HNG) cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF-кB translocation and DNA binding inhibitors, including the chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol analog CAY10512 (trans-3,5,4′-trihydroxystilbene), indicated the NF-кB sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA-146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets, including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH) and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for NF-кB, miRNA-125b and miRNA-146a. These data further indicate that just two NF-кB-mediated miRNAs have tremendous potential to contribute to the regulation of neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling and amyloidogenesis in stressed primary neural cells of the human brain.