Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1519, Dongyue Avenue, Nanchang, Jiangxi Province, 330006, P.R. China.
Orphanet J Rare Dis. 2024 Oct 15;19(1):380. doi: 10.1186/s13023-024-03394-5.
Legg-Calvé-Perthes disease (LCPD) commonly occurs among adolescents, threatening their health. However, the potential mechanism underlying LCPD remains unclear. miR-214-3p is shown as a critical role in LCPD development with unspecified upstream regulators.
Levels of miR-214-3p and circCDR1as in healthy controls and LCPD patients were determined by qRT-PCR. The role of circCDR1as/miR-214-3p axis in LCPD was determined by testing the cell viability and apoptosis in TC28 cells and primary chondrocytes. Regulation between circCDR1as and miR-214-3p was examined by RIP and ChIP assays. The inflammatory response and angiogenesis were evaluated by M2 macrophage polarization and HUVECs tumor formation.
circCDR1as was overexpressed in LCPD patients with a negative correlation with miR-214-3p. Inhibition of circCDR1as alleviated the cell viability and apoptosis of DEX-treated chondrocytes, stimulated M2 macrophage polarization and angiogenesis. miR-214-3p was proved as a downstream effector to participate in circCDR1as mediated actions. circCDR1as recruited PRC2 complex to epigenetically suppress miR-214-3p.
Our study illustrated the role and mechanism of circCDR1as in LCPD development by targeting miR-214-3p, highlighting its potential in the therapy for LCPD.
Legg-Calvé-Perthes 病(LCPD)常见于青少年,威胁其健康。然而,LCPD 的潜在机制尚不清楚。miR-214-3p 在 LCPD 发展中起着关键作用,但上游调节因子尚不清楚。
通过 qRT-PCR 测定健康对照组和 LCPD 患者中 miR-214-3p 和 circCDR1as 的水平。通过检测 TC28 细胞和原代软骨细胞的细胞活力和凋亡来确定 circCDR1as/miR-214-3p 轴在 LCPD 中的作用。通过 RIP 和 ChIP 测定来检查 circCDR1as 和 miR-214-3p 之间的调节关系。通过 M2 巨噬细胞极化和 HUVECs 肿瘤形成评估炎症反应和血管生成。
circCDR1as 在 LCPD 患者中表达上调,与 miR-214-3p 呈负相关。抑制 circCDR1as 可减轻 DEX 处理的软骨细胞的细胞活力和凋亡,刺激 M2 巨噬细胞极化和血管生成。miR-214-3p 被证明是参与 circCDR1as 介导作用的下游效应物。circCDR1as 募集 PRC2 复合物来表观遗传抑制 miR-214-3p。
本研究通过靶向 miR-214-3p 阐明了 circCDR1as 在 LCPD 发展中的作用和机制,突出了其在 LCPD 治疗中的潜力。