Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth

Yongtao Gao,1 Haiyang Qian,2 Xue Tang,1 Xiling Du,3 Gang Wang,2 Hairong Zhang,2 Fei Ye,2 Te Liu41The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Department of Imaging, Dahua Hospi...

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Autores principales:	Gao Y, Qian H, Tang X, Du X, Wang G, Zhang H, Ye F, Liu T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	human endometrial carcinoma stem cells superparamagnetic iron oxide nanoparticles microRNA;succinate receptor 1 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bcb6212b1c414519a02e51c43028e51b
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spelling	oai:doaj.org-article:bcb6212b1c414519a02e51c43028e51b2021-12-02T04:22:59ZSuperparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth1178-2013https://doaj.org/article/bcb6212b1c414519a02e51c43028e51b2019-04-01T00:00:00Zhttps://www.dovepress.com/superparamagnetic-iron-oxide-nanoparticle-mediated-expression-of-mir-3-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yongtao Gao,1 Haiyang Qian,2 Xue Tang,1 Xiling Du,3 Gang Wang,2 Hairong Zhang,2 Fei Ye,2 Te Liu41The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Department of Imaging, Dahua Hospital, Shanghai, 200237, People’s Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 4Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, People’s Republic of ChinaBackground: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive.Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs.Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced.Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.Keywords: human endometrial carcinoma stem cells, superparamagnetic iron oxide nanoparticles, microRNA, succinate receptor 1Gao YQian HTang XDu XWang GZhang HYe FLiu TDove Medical Pressarticlehuman endometrial carcinoma stem cellssuperparamagnetic iron oxide nanoparticlesmicroRNA;succinate receptor 1Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2719-2731 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	human endometrial carcinoma stem cells superparamagnetic iron oxide nanoparticles microRNA;succinate receptor 1 Medicine (General) R5-920
spellingShingle	human endometrial carcinoma stem cells superparamagnetic iron oxide nanoparticles microRNA;succinate receptor 1 Medicine (General) R5-920 Gao Y Qian H Tang X Du X Wang G Zhang H Ye F Liu T Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
description	Yongtao Gao,1 Haiyang Qian,2 Xue Tang,1 Xiling Du,3 Gang Wang,2 Hairong Zhang,2 Fei Ye,2 Te Liu41The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Department of Imaging, Dahua Hospital, Shanghai, 200237, People’s Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 4Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, People’s Republic of ChinaBackground: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive.Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs.Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced.Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.Keywords: human endometrial carcinoma stem cells, superparamagnetic iron oxide nanoparticles, microRNA, succinate receptor 1
format	article
author	Gao Y Qian H Tang X Du X Wang G Zhang H Ye F Liu T
author_facet	Gao Y Qian H Tang X Du X Wang G Zhang H Ye F Liu T
author_sort	Gao Y
title	Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
title_short	Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
title_full	Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
title_fullStr	Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
title_full_unstemmed	Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth
title_sort	superparamagnetic iron oxide nanoparticle-mediated expression of mir-326 inhibits human endometrial carcinoma stem cell growth
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/bcb6212b1c414519a02e51c43028e51b
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Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth

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