Anti­inflammatory role of microRNA­429 in human gingival epithelial cells­inhibition of IL­8 production through direct binding to IKKß mRNA.

ABSTRACT

MicroRNAs (miRNAs), a family of small non­coding RNAs, serve a pivotal role in the regulation of the inflammation by modulating the expression of various genes. However, the molecular mechanism by which miRNAs regulate inflammation­associated molecules in oral epithelial cells remains to be elucidated. The present study examined the biological function of miR­429 by performing the gain­/loss­of­function studies of miR­429 in a gingival squamous cell carcinoma line Ca9­22 cells that either over­ or under­expressed miR­429 through transient transfection with miR­429 mimic or miR­429 inhibitor, respectively. The results demonstrated that the over­expression of miR­429 suppressed the mRNA level of several interleukins, including IL­8. In addition, the over­expression of miR­429 reduced IL­8 secretion under the basal and TNF­α stimulated conditions, whereas the secretion of IL­8 was enhanced when miR­429 was under­expressed. The over­expression of miR­429 inhibited the activation of the transcription factor NF­κB. Furthermore, we found that miR­429 suppressed both mRNA and protein levels of IKKß via its direct binding to the 3'­untranslated region of IKKß mRNA. In addition, the downregulation of IKKß by small interfering RNA reduced both NF­kB activity and IL­8 production in Ca9­22 cells. Taken together, the findings revealed the molecular mechanism of miR­429 to regulate the inflammatory mediator in gingival cells and suggested that it could be useful as a therapeutic target of oral inflammatory diseases.