Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a

Abstract

IL-10 is a key regulator of the immune system that critically determines health and disease. Its expression is finely tuned both at the transcriptional and posttranscriptional levels. Although the importance of posttranscriptional regulation of IL-10 has been previously shown, understanding the underlying mechanisms is still in its infancy. In this study, using a combination of bioinformatics and molecular approaches, we report that microRNA (hsamiR-106a) regulates IL-10 expression. The hsa-miR-106a binding site in the 3 UTR of IL10 has been identified by site-directed mutagenesis studies. Also, the involvement of transcription factors, Sp1 and Egr1, in the regulation of hsa-miR-106a expression and concomitant decrease in the IL-10 expression, has also been demonstrated. In summary, our results showed that IL-10 expression may be regulated by miR-106a, which is in turn transcriptionally regulated by Egr1 and Sp1.Egr1 ͉ IL-10 ͉ microRNA ͉ SP1 ͉ miR-106a promoter

MicroRNA expression patterns in indeterminate inflammatory bowel disease

“…[23][24][25][26] miR-106a posttranscriptionally regulates the expression of interleukine-10 (IL-10), which is a key modulator of the immune system. On the other hand, miR-106a expression is regulated by tumor necrosis factor alpha and lipopolysaccharide.…”

MicroRNAs in the regulation of TLR and RIG-I pathways

“…Il-12p35 mRNA can be targeted by miR-21 in macrophages and DCs, leading to restricted adaptive Th1 responses. [99][100][101] miR-106 has been demonstrated to target Il-10 mRNA, 102 while miR-29 suppresses immune responses against intracellular pathogens by targeting IFN-c. 103 Numerous cytokine encoding mRNAs are regulated by RNA-binding proteins (RBPs) through the AU-rich elements in their 39-UTR, which may play a vital role in mRNA stabilization. MiRNAs can also cooperate with these RBPs to regulate mRNA stability or translation.…”

Investigation of significant microRNA-mRNA pairs associated with nonspecific digestive disorder in rabbits

“…Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3 gene, which could promote inflammation and pathogenesis of UC in children (Koukos et al, 2013). The miR-106a and miR106b decrease IL-10 expression by degrading its mRNA, which is a key antiinflammatory regulator in many model systems (Sharma et al, 2009).…”