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
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:0a143e3c2ac845a7a1cf1cb716e5f6b32021-12-02T16:39:24ZExosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis1178-2013https://doaj.org/article/0a143e3c2ac845a7a1cf1cb716e5f6b32021-08-01T00:00:00Zhttps://www.dovepress.com/exosomal-lncrna-chl1-as1-derived-from-peritoneal-macrophages-promotes--peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Ting 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, MDM2Liu TLiu MZheng CZhang DLi MZhang LDove Medical Pressarticleendometriosisperitoneal macrophagesexosomeslncrna chl1-as1mir-610mdm2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5451-5464 (2021)
institution DOAJ
collection DOAJ
language EN
topic endometriosis
peritoneal macrophages
exosomes
lncrna chl1-as1
mir-610
mdm2
Medicine (General)
R5-920
spellingShingle endometriosis
peritoneal macrophages
exosomes
lncrna chl1-as1
mir-610
mdm2
Medicine (General)
R5-920
Liu T
Liu M
Zheng C
Zhang D
Li M
Zhang L
Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
description 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
format article
author Liu T
Liu M
Zheng C
Zhang D
Li M
Zhang L
author_facet Liu T
Liu M
Zheng C
Zhang D
Li M
Zhang L
author_sort Liu T
title Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
title_short Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
title_full Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
title_fullStr Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
title_full_unstemmed Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis
title_sort exosomal lncrna chl1-as1 derived from peritoneal macrophages promotes the progression of endometriosis via the mir-610/mdm2 axis
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/0a143e3c2ac845a7a1cf1cb716e5f6b3
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