MicroRNA-100 shuttled by human umbilical cord MSC-secreted extracellular vesicles induces endometriosis by inhibiting HS3ST2

Abstract

In recent years, the function of human umbilical cord mesenchymal stem cell-originated extracellular vesicles (hUC-MSC-EVs) on endometriosis has been reported, while its specific mechanisms remain largely unknown. This study aimed at investigating the mechanisms underlying the modulation of EVs harboring miR-100 derived from hUC-MSCs in the growth dynamics of endometrial stromal cells in endometriosis. Endometriosis mouse models were established. miR-100 was upregulated and HS3ST2 was downregulated in endometriosis. Ectopic endometrial tissues and umbilical cord tissues were obtained to extract endometrial stromal cells and hUC-MSCs, from which EVs were isolated. Next, the endometrial stromal cells were co-cultured with hUC-MSC-EVs, during which gain- or loss-of-function approaches were employed for gene overexpression or silencing. The binding affinity among miR-100 and HS3ST2 was identified using multiple assays. It was unveiled that miR-100 could target and inhibit HS3ST2. miR-100 from hUC-MSCs could be transferred into the endometrial stromal cells via EVs. Moreover, miR-100 shuttled by hUC-MSC-EVs facilitated endometrial stromal cell proliferation, invasion, and migration, as well as EMT by inhibiting HS3ST2. In vivo experiments also confirmed that hUC-MSC-derived EVs carrying miR-100 induced the occurrence and development of endometriosis. Collectively, hUC-MSC-EV-loaded miR-100 downregulated HS3ST2 to facilitate the development of endometriosis, which highlights a promising therapeutic target for treating endometriosis.