Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis

Background: Exosomes secreted by peritoneal macrophages (pM9) are deeply involved in the development of endometriosis (EMs). Exosomes can mediate cell-to-cell communication by transferring biological molecules. This study aimed to explore the effect and mechanism of exosomal long non-coding RNA (lncRNA) CHL1-AS1 derived from pM9 on EMs. Materials and Methods: Exosomes (exo) from pM9 were isolated, identified, and co-cultured with ectopic endometrial stromal cells (eESCs) to investigate the biological func-tions of pM9-exo. qRT-PCR was used to detect the expression of lncRNA CHL1-AS1 in pM9-exo from EMs and control patients and verify the transportation of lncRNA CHL1-AS1 from pM9 to eESCs. The effects of exosomal lncRNA CHL1-AS1 on eESC proliferation, migration, invasion, and apoptosis were also detected. The relationships among lncRNA CHL1-AS1, miR-610, and MDM2 (mouse double minute 2) were verified by dual-luciferase reporter assay. The in vivo experiments were conducted to verify the effects of exosomal lncRNA on EMs using a xenograft model of EMs. Results: Exosomes from pM9 were successfully isolated. EMs-pM9-exo promoted eESC proliferation, migration, and invasion and inhibited their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pM9-exo and transported from pM9 to eESCs via exosomes. lncRNA CHL1-AS1 was found to act as a competing endogenous RNA of miR-610 to promote the expression of MDM2. EMs-pM9-exo shuttled lncRNA CHL1-AS1 to promote eESC pro-liferation, migration, and invasion and inhibit apoptosis by downregulating miR-610 and upregulating MDM2. Furthermore, exosomal lncRNA CHL1-AS1 promoted EMs lesions growth by increasing MDM2 in vivo. Conclusion: The results demonstrate that exosomal lncRNA CHL1-AS1 promotes the proliferation, migration, and invasion of eESCs and inhibits their apoptosis by downregulat-ing miR-610 and upregulating MDM2, which might be a potential therapeutic target for EMs.

Automated summary

The study revealed that exosomes derived from pM9 promoted proliferation, migration, and invasion of eESCs, while inhibiting their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pM9-exo and transported from pM9 to eESCs via exosomes. Additionally, lncRNA CHL1-AS1 facilitated the shuttle of EMs-pM9-exo to promote eESC proliferation, migration, and invasion by modulating miR-610 and MDM2.