Background: Exosomes secreted by peritoneal macrophages (pMφ) 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 pMφ on EMs. Materials and Methods: Exosomes (exo) from pMφ were isolated, identified, and co-cultured with ectopic endometrial stromal cells (eESCs) to investigate the biological functions of pMφ-exo. qRT-PCR was used to detect the expression of lncRNA CHL1-AS1 in pMφ-exo from EMs and control patients and verify the transportation of lncRNA CHL1-AS1 from pMφ 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 pMφ were successfully isolated. EMs-pMφ-exo promoted eESC proliferation, migration, and invasion and inhibited their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pMφ-exo and transported from pMφ 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-pMφ-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.
CITATION STYLE
Liu, T., Liu, M., Zheng, C., Zhang, D., Li, M., & Zhang, L. (2021). Exosomal lncrna chl1-as1 derived from peritoneal macrophages promotes the progression of endometriosis via the mir-610/mdm2 axis. International Journal of Nanomedicine, 16, 5451–5464. https://doi.org/10.2147/IJN.S323671
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