Anti‑inflammatory role of microRNA‑429 in human gingival epithelial cells‑inhibition of IL‑8 production through direct binding to IKKβ mRNA

microRNA-429 在人类牙龈上皮细胞中的抗炎作用 - 通过直接结合 IKKβ mRNA 抑制 IL-8 的产生

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作者:Hiromichi Kawasaki, Hirotaka Amano

Abstract

MicroRNAs (miRNAs), a family of small non‑coding 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 inflammation‑associated molecules in oral epithelial cells remains to be elucidated. The present study examined the biological function of miR‑429 by performing the gain‑/loss‑of‑function studies of miR‑429 in a gingival squamous cell carcinoma line Ca9‑22 cells that either over‑ or under‑expressed miR‑429 through transient transfection with miR‑429 mimic or miR‑429 inhibitor, respectively. The results demonstrated that the over‑expression of miR‑429 suppressed the mRNA level of several interleukins, including IL‑8. In addition, the over‑expression of miR‑429 reduced IL‑8 secretion under the basal and TNF‑α stimulated conditions, whereas the secretion of IL‑8 was enhanced when miR‑429 was under‑expressed. The over‑expression of miR‑429 inhibited the activation of the transcription factor NF‑κB. Furthermore, we found that miR‑429 suppressed both mRNA and protein levels of IKKβ via its direct binding to the 3'‑untranslated region of IKKβ mRNA. In addition, the downregulation of IKKβ by small interfering RNA reduced both NF‑kB activity and IL‑8 production in Ca9‑22 cells. Taken together, the findings revealed the molecular mechanism of miR‑429 to regulate the inflammatory mediator in gingival cells and suggested that it could be useful as a therapeutic target of oral inflammatory diseases.

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