粉防己碱诱导lncRNA NEAT1下调通过STAT3/miR-17-5p途径抑制类风湿关节炎进展。
Tetrandrine-induced downregulation of lncRNA NEAT1 inhibits rheumatoid arthritis progression through the STAT3/miR-17-5p pathway.
作者信息
Duan Bo, Yu Zhao, Liu Ruilin, Li Jigao, Song Zhe, Zhou Quan, Chen Lichuan
机构信息
Department of Rheumatology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China.
Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
出版信息
Immunopharmacol Immunotoxicol. 2022 Dec;44(6):886-893. doi: 10.1080/08923973.2022.2092748. Epub 2022 Jul 11.
BACKGROUND
The inhibitory effect of Tetrandrine (Tet) on rheumatoid arthritis (RA) is well established. However, its exact molecular mechanism remains unknown.
METHODS
RT-qPCR coupled with western blotting was employed to analyze the expression of NEAT1, miR-17-5p, and STAT3 in RA tissues and/or RA-fibroblast-like synoviocytes (RA-FLS) treated with 3 μmol/L of Tet for 48 h. Cell Counting Kit-8 assay and flow cytometry were performed to assess RA-FLS proliferation and apoptosis. Luciferase reporter assays were used to validate the interactions between miR-17-5p and STAT3 or NEAT1.
RESULTS
The expression of NEAT1 decreased in a time-dependent manner upon Tet treatment. Tet significantly inhibited RA-FLS proliferation and triggered apoptosis by downregulating NEAT1 expression. Additionally, NEAT1 directly targeted miR-17-5p to upregulate STAT3 expression. Tet-induced low NEAT1 expression impaired RA-FLS growth by targeting miR-17-5p and inhibiting STAT3.
CONCLUSION
Tet exerts its inhibitory role in RA progression by regulating the NEAT1/miR-17-5p/STAT3 pathway.
背景
粉防己碱（Tet）对类风湿关节炎（RA）的抑制作用已得到充分证实。然而，其确切的分子机制仍不清楚。
方法
采用逆转录定量聚合酶链反应（RT-qPCR）结合蛋白质免疫印迹法，分析用3μmol/L粉防己碱处理48小时的RA组织和/或RA成纤维样滑膜细胞（RA-FLS）中NEAT1、miR-17-5p和信号转导与转录激活因子3（STAT3）的表达。进行细胞计数试剂盒-8（Cell Counting Kit-8）检测和流式细胞术，以评估RA-FLS的增殖和凋亡。荧光素酶报告基因检测用于验证miR-17-5p与STAT3或NEAT1之间的相互作用。
结果
粉防己碱处理后，NEAT1的表达呈时间依赖性下降。粉防己碱通过下调NEAT1表达显著抑制RA-FLS增殖并引发凋亡。此外，NEAT1直接靶向miR-17-5p以上调STAT3表达。粉防己碱诱导的低NEAT1表达通过靶向miR-17-5p并抑制STAT3来损害RA-FLS的生长。
结论
粉防己碱通过调节NEAT1/miR-17-5p/STAT3通路在RA进展中发挥抑制作用。
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