Down-regulation of Exosomal miR-214-3p Targeting CCN2 Contributes to Endometriosis Fibrosis and the Role of Exosomes in the Horizontal Transfer of miR-214-3p

Zhang, Yanqin; Chang, Xiangyu; Wu, Di; Deng, Mengqi; Miao, Jinwei; Jin, Zhaoyu

doi:10.1007/s43032-020-00350-z

Cited by 26 publications

(34 citation statements)

References 35 publications

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“…Zhao et al found that miR-194-5p repressed cell progression and promoted cell apoptosis of ectopic endometrial cells by modulating STAT1/mTOR signaling pathway [ 15 ]. Moreover, exosomal miR-214-3p suppressed cell fibrosis in EM by targeting CCN2, suggesting that miR-214-3p may be a biomarker for EM therapy [ 16 ]. miR-206 has been reported to be a therapy biomarker in CC [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

miR-206 Targets MALAT1 to Suppress Cell Progression of Ectopic Endometrial Stromal Cells in Endometriosis

Guan

et al. 2022

Journal of Healthcare Engineering

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Background. miR-206 was reported to be a tumor suppressor in bladder cancer. In this study, we explore the expression and function of miR-206 in endometriosis (EM). Methods. 40 EM patients undergoing total hysterectomy were selected as the experimental group. RT-qPCR assay was adopted to detect the expression of MALAT1 and miR-206 in EM. Cell proliferation was detected by EdU incorporation and colony formation assay. Cell migration and invasion viability of ESCs were examined by transwell assay and wound healing assay. Flow cytometry was carried out to assess cell apoptosis of ESCs. The protein expressions of Bcl-2 and Bax were examined by western blot assay. The relationship between miR-206 and MALAT1 was verified by the dual-luciferase reporter assay and RNA pull-down assay. Results. In this work, miR-206 was found to be downregulated in EM. Functional experiments displayed that miR-206 mimic repressed cell proliferation, migration, and invasion of ESCs and promoted cell apoptosis of ESCs. Furthermore, miR-206 mimic reduced the expression of Bcl-2 but enhanced the expression of Bax. MALAT1 was found to be upregulated in EM. Furthermore, MALAT1 was indicated to be a target of miR-206. Additionally, MALAT1 was found to alleviate the influence of miR-206 on cell progression of ESCs. Furthermore, miR-206 inhibited tumor growth in vivo. Conclusion. This study indicated that miR-206 inhibited cell progression by regulating MALAT1 in EM. Hence, miR-206 was suggested to be a possible target for EM treatment.

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Section: Discussionmentioning

confidence: 99%

miR-206 Targets MALAT1 to Suppress Cell Progression of Ectopic Endometrial Stromal Cells in Endometriosis

Guan

et al. 2022

Journal of Healthcare Engineering

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“…Extracellular vesicles (EVs), especially exosomes, have been well-established to deliver microRNAs (miRNAs), proteins, and lipids, and the cargos have been assumed to work cooperatively to modulate tumor microenvironment [ 9 ]. Intriguingly, evidence exists suggesting that exosomes secreted by ectopic endometrial stromal cells could restrict the fibrosis in EMs by delivering a typical miRNA, miR-214 [ 10 , 11 ]. Further, another miRNA, miR-30c, has been highlighted for notably downregulated expression in ectopic and eutopic endometriosis tissues [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

et al. 2022

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Endometriosis (EMs) is a benign gynecological disorder showing some tumor-like migratory and invasive phenotypes. This study intended to investigate the role of microRNA-30c (miR-30c) in EMs, which is involved with B-cell lymphoma 9 (BCL9), an activator of the Wnt/β-catenin signaling pathway. EMs specimens were clinically collected for determination of miR-30c and BCL9 expression. Exosomes were isolated from endometrial epithelial cells (EECs), and the uptake of exosomes by ectopic EECs (ecto-EECs) was characterized using fluorescence staining and confocal microscopy. The binding of miR-30c to BCL9 was validated by dual-luciferase reporter assay. Artificial modulation (up- and down-regulation) of the miR-30c/BCL9/Wnt/CD44 regulatory cascade was performed to evaluate its effect on ecto-EEC invasion and migration, as detected by Transwell and wound healing assays. A mouse model of EMs was further established for in vivo substantiation. Reduced miR-30c expression and elevated BCL9 expression was revealed in EMs ectopic tissues and ecto-EECs. Normal EECs-derived exosomes delivered miR-30c to ecto-EECs to suppress their invasive and migratory potentials. Then, miR-30c was observed to inhibit biological behaviors of ecto-EECs by targeting BCL9, and the miR-30c-induced inhibitory effect was reversed by BCL9 overexpression. Further, miR-30c diminished the invasion and migration of ecto-EECs by blocking the BCL9/Wnt/CD44 axis. Moreover, miR-30c-loaded exosomes attenuated the metastasis of ecto-EEC ectopic nodules. miR-30c delivered by EECs-derived exosomes repressed BCL9 expression to block the Wnt/β-catenin signaling pathway, thus attenuating the tumor-like behaviors of ecto-EECs in EMs.

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“…miR-15a-5p was poorly expressed in EMS. Similarly, level of exosomal miR-214-3p in EMS patients’ serum was lower than that of non-EMS patient [ 19 ]. Moreover, overexpression of miR-214 offers an alternative therapeutic approach for EMS fibrosis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal AFAP1-AS1 binds to microRNA-15a-5p to promote the proliferation, migration, and invasion of ectopic endometrial stromal cells in endometriosis

Wang

Zhang

Jiang

et al. 2022

Reprod Biol Endocrinol

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Background Endometriosis (EMS) remains a major challenge to reproductive health due to multifactorial etiology, disease heterogeneity, and the lack of appropriate diagnostic markers and treatment. Eexosome (Exo) has become a major factor in progression of a variety of diseases. However, the mechanisms directing their role in the pathophysiology of EMS are ill-defined. Here, we aimed to investigate the clinical implications of actin filament associated protein 1-Antisense RNA 1 (AFAP1-AS1) in EMS. Methods Bioinformatics analysis was used to predict the expression and interaction of AFAP1-AS1, miR-15a-5p and BCL9 in EMS, and dual luciferase reporter assay was used to verify the targeted relationship of AFAP1-AS1, miR-15a-5p, and BCL9. The Exo from endometrial stromal cells (ESCs) was isolated and characterized by transmission electron microscopy (TEM) and Nanoparticle tracking analysis (NTA). Exosome uptake studies were performed. For in vitro assay, ectopic ESCs (EcESCs) proliferation, migration, and invasion were assessed by CCK-8 and Transwell assays. In vivo assay was performed by establishment of EMS mice to validate the result derived from in vitro assay. Results The Exo was successfully isolated from ESCs and we observed high expression of AFAP1-AS1 and BCL9 but low expression of miR-15a-5p in EMS. Moreover, Exo derived from EcESCs could deliver AFAP1-AS1 to EcESCs and thus promoting proliferation, migration, and invasion of ESCs. AFAP1-AS1 bound to BCL9, which was targeted by miR-15a-5p in EMS. In vivo experiments in nude mice revealed that inhibition of Exosomal AFAP1-AS1 suppressed migration and invasion of EcESCs through miR-15a-5p/BCL9. Conclusions Collectively, these findings suggested that ESCs-derived Exo carrying AFAP1-AS1 contributed to EMS pathogenesis. This study might help us realize the etiology of EMS and improve the treatment of the related complications.

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Down-regulation of Exosomal miR-214-3p Targeting CCN2 Contributes to Endometriosis Fibrosis and the Role of Exosomes in the Horizontal Transfer of miR-214-3p

Cited by 26 publications

References 35 publications

miR-206 Targets MALAT1 to Suppress Cell Progression of Ectopic Endometrial Stromal Cells in Endometriosis

miR-206 Targets MALAT1 to Suppress Cell Progression of Ectopic Endometrial Stromal Cells in Endometriosis

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

Exosomal AFAP1-AS1 binds to microRNA-15a-5p to promote the proliferation, migration, and invasion of ectopic endometrial stromal cells in endometriosis

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