lncRNA TUG1 promotes endometrial fibrosis and inflammation by sponging miR-590-5p to regulate Fasl in intrauterine adhesions
lncRNA TUG1 promotes endometrial fibrosis and inflammation by sponging miR-590-5p to regulate Fasl in intrauterine adhesions
复制标题
DOI：
10.1016/j.intimp.2020.106703
复制
发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Feng, Yun
中科院分区：
文献类型：
--
作者：
Ai, Ying;Chen, Mingqing;Feng, Yun
子宫内粘连（IUA）是世界范围内女性最常见的生殖系统疾病之一。lncRNA在多种疾病中的作用已被证实，但lncRNA牛磺酸上调基因1（TUG 1）在IUA发生发展中的作用及机制尚需进一步阐明。在这里，我们发现lncRNA TUG 1在IUA和TGF-β 1处理的人胚胎干细胞（hESC）的子宫内膜组织中上调。此外，lncRNA TUG 1沉默减轻了TGF-β 1诱导的hESC的增殖和迁移能力，并增强了体外炎性细胞因子的分泌。体内实验表明，抑制lncRNA TUG 1可通过下调炎症反应和上皮-间质转化（EMT）过程促进IUA大鼠子宫内膜再生。在机制上，lncRNA TUG 1抑制通过竞争性结合miR-590- 5 p以下调Fas 1表达来减弱EMT过程和炎症。总之，我们的研究结果为解释lncRNA TUG 1/miR-590- 5 p/FasL轴在IUA进展中的机制提供了重要的理论证据，并可能为IUA患者的治疗提供新的生物标志物。
Intrauterine adhesion (IUA) is one of the most common reproductive system diseases in women worldwide. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA taurine upregulated gene 1 (TUG1) in the progression of IUA need to be elucidated further. Here, we found that lncRNA TUG1 was upregulated in the endometrial tissues of IUA and TGF-beta 1-treated human embryonic stem cells (hESCs). Moreover, lncRNA TUG1-silenced alleviated TGF-beta 1-induced the proliferation and migration abilities of hESCs and enhanced inflammatory cytokines secretion in vitro. In vivo experiments showed that inhibition of lncRNA TUG1 promoted endometrium regeneration in IUA rats through downregulating inflammatory response and epithelial-to-mesenchymal transition (EMT) process. Mechanistically, lncRNA TUG1 suppression attenuated EMT process and inflammation through competitively binding miR-590-5p to downregulate Fasl expression. Collectively, our findings provide vital theoretical evidence for explaining the mechanisms of the lncRNA TUG1/miR-590-5p/Fasl axis in the progression of IUA, and may provide a new biomarker for the treatment of IUA patients.