Department of Spinal-Surgery, Jining No.1 People's Hospital (Jining First People's Hospital Affiliated to Jining Medical University), Jining, Shandong, China.
Department of Neurosurgery, Jining No.1 People's Hospital (Jining First People's Hospital Affiliated to Jining Medical University), Jining, Shandong, China.
Mol Cell Biochem. 2020 Mar;466(1-2):17-24. doi: 10.1007/s11010-019-03681-x. Epub 2020 Jan 1.
Ankylosing spondylitis (AS) is a progressive systemic disease characterized by chronic inflammation response of the sacroiliac joint and spine. Long non-coding RNAs (lncRNAs) are widely involved in the regulation of various diseases. However, the role of lncRNA maternally expressed gene 3 (MEG3) in the inflammatory response of AS has not been studied. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues and cells. The expression levels of MEG3, microRNA-146a (miR-146a), and inflammatory cytokines were measured by quantitative real-time PCR (qRT-PCR). Correlation between MEG3 or miR-146a and inflammatory cytokines was analyzed by Pearson analysis. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to clarify the interaction between MEG3 and miR-146a. MEG3 was downregulated in AS patients, negatively correlated with the levels of IL-1β, IL-6, and TNF-α, and blocked the inflammatory response of AS. MiR-146a was upregulated in AS patients and could interact with MEG3. The expression of miR-146a was positively correlated with IL-1β, IL-6, and TNF-α levels. Overexpression of miR-146a reversed the inhibitory effect of abnormal MEG3 expression on inflammatory cytokines. LncRNA MEG3 plays an anti-inflammatory role in AS partially through targeting miR-146a, which provides a potential new means for the treatment of AS patients.
强直性脊柱炎(AS)是一种以骶髂关节和脊柱慢性炎症反应为特征的进行性系统性疾病。长链非编码 RNA(lncRNA)广泛参与各种疾病的调控。然而,lncRNA 母系表达基因 3(MEG3)在 AS 炎症反应中的作用尚未研究。酶联免疫吸附试验(ELISA)用于检测组织和细胞中炎症细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。通过实时定量 PCR(qRT-PCR)测量 MEG3、微小 RNA-146a(miR-146a)和炎症细胞因子的表达水平。通过 Pearson 分析分析 MEG3 或 miR-146a 与炎症细胞因子之间的相关性。双荧光素酶报告和 RNA 免疫沉淀(RIP)测定用于阐明 MEG3 和 miR-146a 之间的相互作用。AS 患者中 MEG3 下调,与 IL-1β、IL-6 和 TNF-α水平呈负相关,并阻断 AS 的炎症反应。AS 患者中 miR-146a 上调,可与 MEG3 相互作用。miR-146a 的表达与 IL-1β、IL-6 和 TNF-α水平呈正相关。miR-146a 的过表达逆转了异常 MEG3 表达对炎症细胞因子的抑制作用。LncRNA MEG3 在 AS 中发挥抗炎作用部分是通过靶向 miR-146a,为 AS 患者的治疗提供了一种新的潜在手段。