Department of Gynaecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, Henan Province, China.
Endocrinology. 2022 May 1;163(5). doi: 10.1210/endocr/bqac033.
Adenomyosis (AM) is a common gynecological disorder that can cause pelvic pain. The regulatory role of long noncoding RNAs (lncRNAs) in AM progression has been widely reported. This study investigated the effect and mechanism of lncRNA taurine-upregulated gene 1 (TUG1) on endometrial epithelial cells (EECs) in AM.
Endometrial tissues of AM patients and controls were collected. A murine model of AM was established by tamoxifen induction. TUG1 expression in endometrial tissues of AM patients and mice was determined. In vivo, the effect of TUG1 on AM mice was measured through H&E staining, Masson's staining, uterine weight, and estradiol concentration. EECs isolated from AM patients were transfected with sh-TUG1. In vitro, the effect of TUG1 on the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis of EECs was evaluated by CCK8, colony formation, immunofluorescence, wound healing, and Transwell assays. The binding relationship among TUG1, E2F4, and KLF5 was confirmed using RNA immunoprecipitation and RNA pull-down assays. A function rescue experiment was designed to verify the effect of KLF5 on EECs.
TUG1 expression was elevated in AM mice and patients. Downregulation of TUG1 promoted the recovery of AM mice. Downregulation of TUG1 suppressed proliferation, migration, invasion, EMT, and angiogenesis of EECs. Mechanically, TUG1 suppressed KLF5 transcription by binding to E2F4. Downregulation of KLF5 reversed the inhibitory effect of TUG1 silencing on the functions of EECs.
TUG1 expression was elevated in AM, and TUG1 facilitated proliferation, migration, invasion, EMT, and angiogenesis of EECs via E2F4/KLF5, thereby aggravating AM.
子宫腺肌病（AM）是一种常见的妇科疾病，可引起盆腔疼痛。长链非编码 RNA（lncRNA）在 AM 进展中的调控作用已被广泛报道。本研究探讨了 lncRNA 牛磺酸上调基因 1（TUG1）对 AM 中子宫内膜上皮细胞（EEC）的作用及机制。
收集 AM 患者和对照者的子宫内膜组织。通过他莫昔芬诱导建立 AM 小鼠模型。检测 AM 患者和小鼠子宫内膜组织中 TUG1 的表达。体内实验中，通过 H&E 染色、Masson 染色、子宫重量和雌二醇浓度检测 TUG1 对 AM 小鼠的影响。从 AM 患者中分离出 EECs 并转染 sh-TUG1。体外实验中，通过 CCK8 法、集落形成实验、免疫荧光法、划痕愈合实验和 Transwell 实验评估 TUG1 对 EECs 增殖、迁移、侵袭、上皮间质转化（EMT）和血管生成的影响。采用 RNA 免疫沉淀和 RNA 下拉实验验证 TUG1、E2F4 和 KLF5 之间的结合关系。设计功能拯救实验验证 KLF5 对 EECs 的作用。
TUG1 在 AM 小鼠和患者中表达上调。下调 TUG1 可促进 AM 小鼠的恢复。下调 TUG1 抑制 EECs 的增殖、迁移、侵袭、EMT 和血管生成。机制上，TUG1 通过与 E2F4 结合抑制 KLF5 的转录。下调 KLF5 逆转了 TUG1 沉默对 EECs 功能的抑制作用。
TUG1 在 AM 中表达上调，TUG1 通过 E2F4/KLF5 促进 EECs 的增殖、迁移、侵袭、EMT 和血管生成，从而加重 AM。
