长链非编码 RNA HULC 的下调通过减少 miR-556-5p 介导的 YAP1 表达抑制强直性脊柱炎中的炎症反应。
Down-regulation of long noncoding RNA HULC inhibits the inflammatory response in ankylosing spondylitis by reducing miR-556-5p-mediated YAP1 expression.
机构信息
Department of Rheumatology, Ganzhou People's Hospital, Ganzhou City, 341000, Jiangxi Province, China.
Department of Emergency, Ganzhou People's Hospital, Ganzhou City, 341000, Jiangxi Province, China.
出版信息
J Orthop Surg Res. 2023 Jul 31;18(1):551. doi: 10.1186/s13018-023-04003-0.
OBJECTIVE
Ankylosing spondylitis (AS) is a progressive systemic disease characterized by a chronic inflammatory response in the sacroiliac joints and spine. Long noncoding RNAs suggest significant actions in the progression of AS. Therefore, a specific lncRNA, highly upregulated in liver cancer (HULC), was studied here regarding its functions and related mechanisms in AS.
METHODS
Measurements of miR-556-5p, HULC, and YAP1 expression were performed on AS cartilage tissues and chondrocytes. The interaction between miR-556-5p and HULC or YAP1 was verified. CCK-8, flow cytometry and enzyme-linked immunosorbent assay were used to evaluate the effects of HULC, miR-556-5p, and YAP1 on the proliferation, apoptosis, and inflammatory response of AS chondrocytes. Furthermore, the action of HULC/miR-556-5p/YAP1 was experimentally observed in AS mice.
RESULTS
HULC and YAP1 levels were augmented, while miR-556-5p levels were suppressed in AS cartilage tissues and chondrocytes. Downregulating HULC or upregulating miR-556-5p stimulated chondrocyte proliferation and inhibited apoptosis and inflammation in AS. miR-556-5p was a downstream factor of HULC, and YAP1 was a potential target of miR-556-5p. The improvement effect of downregulated HULC on AS chondrocytes was saved when YAP1 expression was forced. In addition, silence of HULC improved the pathological injury of spinal cartilage in AS mice by enhancing miR-556-5p-related regulation of YAP1.
CONCLUSION
HULC inhibition relieves the inflammatory response in AS by reducing miR-556-5p-mediated YAP1 expression.
目的
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 在 AS 的进展中具有重要作用。因此，本文研究了在肝癌中高表达的特定长链非编码 RNA（HULC）在 AS 中的功能及其相关机制。
方法
检测 AS 软骨组织和软骨细胞中 miR-556-5p、HULC 和 YAP1 的表达。验证 miR-556-5p 与 HULC 或 YAP1 的相互作用。CCK-8、流式细胞术和酶联免疫吸附试验用于评估 HULC、miR-556-5p 和 YAP1 对 AS 软骨细胞增殖、凋亡和炎症反应的影响。此外，在 AS 小鼠中观察 HULC/miR-556-5p/YAP1 的作用。
结果
AS 软骨组织和软骨细胞中 HULC 和 YAP1 水平升高，而 miR-556-5p 水平降低。下调 HULC 或上调 miR-556-5p 可刺激软骨细胞增殖，抑制 AS 软骨细胞凋亡和炎症。miR-556-5p 是 HULC 的下游因子，YAP1 是 miR-556-5p 的潜在靶点。当 YAP1 表达被强制时，下调 HULC 对 AS 软骨细胞的改善作用被挽救。此外，沉默 HULC 通过增强 miR-556-5p 对 YAP1 的相关调节来改善 AS 小鼠脊柱软骨的病理损伤。
结论
HULC 抑制通过减少 miR-556-5p 介导的 YAP1 表达缓解 AS 中的炎症反应。
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