Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis

作者：Mengjie Yang, Hong Jiang, Xinyu Ding, Lu Zhang, Huaying Zhang, Jiahao Chen, Lijun Li, Xinqin He, Zhixiong Huang, Qionghua Chen · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05245-0 · 被引用次数：18 · 研究领域：Endometriosis Research and Treatment、Reproductive System and Pregnancy、Connective Tissue Growth Factor Research

BACKGROUND: Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. METHODS: We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson's correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. RESULTS: Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further m...