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

Ting Liu,1 Mei Liu,2 Caihua Zheng,3 Daoyan Zhang,4 Mingbao Li,1 Lu Zhang1 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Obstetrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine,...

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Autores principales: Liu T, Liu M, Zheng C, Zhang D, Li M, Zhang L
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2021
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Acceso en línea:https://doaj.org/article/0a143e3c2ac845a7a1cf1cb716e5f6b3
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Sumario:Ting Liu,1 Mei Liu,2 Caihua Zheng,3 Daoyan Zhang,4 Mingbao Li,1 Lu Zhang1 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Obstetrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 3Department of Obstetrics, Changle County Hospital of Traditional Chinese Medicine, Changle, 262400, People’s Republic of China; 4Department of Obstetrics and Gynecology, People’s Hospital of Qihe County, Qihe, 251100, People’s Republic of ChinaCorrespondence: Lu ZhangDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan, Shandong Province, 250012, People’s Republic of ChinaEmail zhangshi908@163.comBackground: Exosomes secreted by peritoneal macrophages (pM&phis;) 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 pM&phis; on EMs.Materials and Methods: Exosomes (exo) from pM&phis; were isolated, identified, and co-cultured with ectopic endometrial stromal cells (eESCs) to investigate the biological functions of pM&phis;-exo. qRT-PCR was used to detect the expression of lncRNA CHL1-AS1 in pM&phis;-exo from EMs and control patients and verify the transportation of lncRNA CHL1-AS1 from pM&phis; 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 pM&phis; were successfully isolated. EMs-pM&phis;-exo promoted eESC proliferation, migration, and invasion and inhibited their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pM&phis;-exo and transported from pM&phis; 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-pM&phis;-exo shuttled lncRNA CHL1-AS1 to promote eESC proliferation, 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 downregulating miR-610 and upregulating MDM2, which might be a potential therapeutic target for EMs.Keywords: endometriosis, peritoneal macrophages, exosomes, lncRNA CHL1-AS1, miR-610, MDM2