Medical College of Soochow University, Soochow, 215006, Jiangsu, People's Republic of China.
Department of Plastic and Hand Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158# Shangtang Rd., Hangzhou, 310014, Zhejiang, People's Republic of China.
Mol Biotechnol. 2022 Apr;64(4):424-433. doi: 10.1007/s12033-021-00419-3. Epub 2021 Oct 29.
Tendon adhesion is the biggest obstacle to repair of tendon injury. Long-chain non-coding RNA X-inactive specific transcript (lncRNA XIST) is highly expressed in populations at high risk of tendon injury. However, whether XIST participates in tendon injury and the specific mechanism remain unknown. Here, we aimed to explore the effects and underlying mechanism of XIST in tendon injury. A mouse model of tendon injury was constructed by the transection method in vivo. XIST and COX2 were highly expressed in tendon tissues of mice with tendon injury, while miR-26a-5p was lowly expressed. Fibroblasts were isolated from tendon injury mice. Overexpression of XIST promoted fibroblast proliferation and upregulated α-SMA and Collagen I protein expression, while silencing XIST indicated the opposite effects. Further dual-luciferase reporter gene assay and RIP assay verified a targeting relationship between XIST and miR-26a-5p, as well as miR-26a-5p and COX2, and XIST targeted miR-26a-5p to act on COX2 expression. miR-26a-5p inhibition and COX2 overexpression reversed the decrease in fibroblast proliferation and the downregulation of α-SMA and Collagen I expression caused by XIST silencing, while interference with si-COX2 eliminated the effects of miR-26a-5p inhibitor. This study revealed that XIST promoted fibroblast proliferation and the formation of tendon adhesion through miR-26a-5p/COX2 pathway, suggesting that XIST/miR-26a-5p/COX2 may be a potential target for the treatment of tendon injury.
肌腱粘连是肌腱损伤修复的最大障碍。长链非编码 RNA X 染色体失活特异性转录物（lncRNA XIST）在肌腱损伤高危人群中高度表达。然而，XIST 是否参与肌腱损伤以及具体机制尚不清楚。在这里，我们旨在探讨 XIST 在肌腱损伤中的作用及其潜在机制。通过体内横切法构建了肌腱损伤的小鼠模型。XIST 和 COX2 在肌腱损伤小鼠的肌腱组织中高表达，而 miR-26a-5p 低表达。从肌腱损伤小鼠中分离出成纤维细胞。过表达 XIST 促进成纤维细胞增殖，并上调α-SMA 和 Collagen I 蛋白表达，而沉默 XIST 则显示出相反的效果。进一步的双荧光素酶报告基因检测和 RIP 实验验证了 XIST 与 miR-26a-5p 以及 miR-26a-5p 与 COX2 之间的靶向关系，并且 XIST 靶向 miR-26a-5p 以作用于 COX2 表达。miR-26a-5p 抑制和 COX2 过表达逆转了 XIST 沉默引起的成纤维细胞增殖减少以及α-SMA 和 Collagen I 表达下调，而干扰 si-COX2 则消除了 miR-26a-5p 抑制剂的作用。这项研究揭示了 XIST 通过 miR-26a-5p/COX2 通路促进成纤维细胞增殖和肌腱粘连的形成，提示 XIST/miR-26a-5p/COX2 可能成为治疗肌腱损伤的潜在靶点。
