The miR-15b-5p/miR-379-3p-FOXO axis regulates cell cycle and apoptosis in scleral remodeling during experimental myopia

作者：Ruixue Zhang, Ying Wen, Jinpeng Liu, Jiawen Hao, Yuan Peng, Miao Zhang, Yunxiao Xie, Zhaohui Yang, Xuewei Yin, Yongwei Shi, Hongsheng Bi, Dadong Guo · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05523-x · 被引用次数：18 · 研究领域：Ophthalmology and Visual Impairment Studies、Corneal surgery and disorders、Scoliosis diagnosis and treatment

BACKGROUND: Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia. METHODS: The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling. RESULTS: miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addit...