Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba 279-0021, Japan.
Department of Internal Medicine and Rheumatology, School of Medicine, Juntendo University, Tokyo 113-8421, Japan.
Int J Mol Sci. 2019 Feb 14;20(4):809. doi: 10.3390/ijms20040809.
MicroRNA (miRNA) is small RNA of 20 to 22 nucleotides in length and is stably present in plasma. Regulating the expression of miRNA taken into cells has been suggested as a general therapeutic approach. We identified the novel anti-inflammatory miRNA hsa-miR-766-3p and investigated its biological function in human rheumatoid arthritis (RA) fibroblast-like synoviocyte MH7A cells. To verify the function of the miRNA present in the plasma of RA patients, we performed a comprehensive analysis of the miRNA expression during abatacept treatment and identified eight miRNAs with significantly altered expression levels. Among these eight miRNAs, miR-766-3p was found to have a clear function. The expression of inflammatory genes in response to inflammatory stimuli was suppressed in MH7A transduced with miR-766-3p. We showed that miR-766-3p indirectly reduced the activation of NF-κB and clarified that this mechanism was partially involved in the reduction of the mineralocorticoid receptor expression. In addition, the inflammatory responses were suppressed in other types of cells. These results indicate the novel function of miR-766-3p, findings that may aid in the development of therapies to suppress inflammation, not only in RA but also in other diseases.
微小 RNA(miRNA)是长度为 20 到 22 个核苷酸的小 RNA,并且在血浆中稳定存在。有人提出,调节细胞内 miRNA 的表达可以作为一种通用的治疗方法。我们鉴定了新型抗炎 miRNA hsa-miR-766-3p,并研究了其在人类类风湿关节炎(RA)成纤维样滑膜细胞 MH7A 中的生物学功能。为了验证 RA 患者血浆中存在的 miRNA 的功能,我们在 abatacept 治疗期间对 miRNA 的表达进行了全面分析,鉴定了 8 个表达水平明显改变的 miRNA。在这 8 个 miRNA 中,miR-766-3p 具有明确的功能。MH7A 转染 miR-766-3p 后,炎症刺激引起的炎症基因表达受到抑制。我们表明,miR-766-3p 间接降低了 NF-κB 的激活,并阐明该机制部分参与了糖皮质激素受体表达的降低。此外,其他类型的细胞中的炎症反应也受到抑制。这些结果表明 miR-766-3p 具有新的功能,这一发现可能有助于开发抑制炎症的治疗方法,不仅在 RA 中,而且在其他疾病中也可能有应用。