The majority of human miRNA genes is transcribed by polymerase II and can be 
classified as class II genes similar to protein-coding genes. Whereas current 
research on miRNAs has focused on the physiological and pathological functions, 
the molecular mechanisms underlying their transcriptional regulation are largely 
unknown. We recently reported that lipopolysaccharide (LPS) alters mature miRNA 
expression profile in human biliary epithelial cells. In this study, we tested 
the role of transcription factor NF-kappaB in LPS-induced transcription of 
select miRNA genes. Of the majority of LPS-up-regulated mature miRNAs in 
cultured human biliary epithelial cells, potential NF-kappaB binding sites were 
identified in the putative promoter elements of their corresponding genes. 
Inhibition of NF-kappaB activation by SC-514, an IKK2 inhibitor, blocked 
LPS-induced up-regulation of a subset of pri-miRNAs, including pri-miR-17-92, 
pri-miR-125b-1, pri-miR-21, pri-miR-23b-27b-24-1, pri-miR-30b, pri-miR-130a and 
pri-miR-29a. Moreover, direct binding of NF-kappaB p65 subunit to the promoter 
elements of mir-17-92, mir-125b-1, mir-21, mir-23b-27b-24-1, mir-30b and 
mir-130a genes was identified by chromatin immunoprecipitation analysis and 
confirmed by the luciferase reporter assay. Thus, a subset of miRNA genes is 
regulated in human biliary epithelial cells through NF-kappaB activation induced 
by LPS, suggesting a role of the NF-kappaB pathway in the transcriptional 
regulation of miRNA genes.