Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.
Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.
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Circ_0088194 通过 miR-766-3p/MMP2 轴促进类风湿关节炎成纤维细胞样滑膜细胞的侵袭和迁移
DOI：
10.3389/fimmu.2021.628654
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Cai Y;Liang R;Xiao S;Huang Q;Zhu D;Shi GP;Ouyang Q;Yang M
环状RNA（circRNA）的失调涉及多种人类疾病。成纤维细胞样滑膜细胞（FLS），形成关节的衬里，表观遗传学上具有侵略性表型，并有助于类风湿性关节炎（RA）的关节破坏。在本研究中，我们鉴定了一种新的circRNA，Circ_0088194，它在RA成纤维细胞样滑膜细胞（RA-FLS）中上调，并与28个关节的疾病活动评分相关。Circ_0088194的过表达促进RA-FLS的迁移和侵袭，而Circ_0088194的抑制具有相反的效果。在机制上，Circ_0088194充当miR-766- 3 p海绵以减轻miR-766 - 3 p对其靶MMP 2（编码基质金属蛋白酶2）的抑制作用，从而促进迁移和侵袭。在RA-FLS中，Circ_0088194的表达水平与miR-766- 3 p的表达水平呈负相关。重要的是，miR-766- 3 p的过表达部分阻断了Circ_0088194过表达诱导的迁移和侵袭。总的来说，这项研究鉴定了一种新的circRNA Circ_0088194，其通过miR-766- 3 p/MMP 2轴促进RA-FLS侵袭和迁移。Circ_0088194可能是防治RA的新靶点。
Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.
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