LAUSR

OBJECTIVES Adenomyosis (AM) is a common gynecological disorder that can cause pelvic pain. The regulatory role of long non-coding RNAs (lncRNAs) in AM progression has been widely reported. This study investigated the effect and mechanism of lncRNA TUG1 on endometrial epithelial cells (EECs) in AM. METHODS 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 HE 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 CCK-8, 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. Function rescue experiment was designed to verify the effect of KLF5 on EECs. RESULTS 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. CONCLUSIONS TUG1 expression was elevated in AM, and TUG1 facilitated proliferation, migration, invasion, EMT, and angiogenesis of EECs via E2F4/KLF5, thereby aggravating AM.