Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

Wenlin Bai,1,2,* Yujiao Chen,1,2,* Pengling Sun,1,2 Ai Gao1,2 1Department of Occupational Health and Environmental Health, School of Public Health, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China *These authors contribu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bai W, Chen Y, Sun P, Gao A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Titanium dioxide nanoparticles autophagy miR34a Bcl-2 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a9b178ab36984be9aa94da034a9a08a8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a9b178ab36984be9aa94da034a9a08a8
record_format	dspace
spelling	oai:doaj.org-article:a9b178ab36984be9aa94da034a9a08a82021-12-02T07:13:44ZDownregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells1178-2013https://doaj.org/article/a9b178ab36984be9aa94da034a9a08a82016-05-01T00:00:00Zhttps://www.dovepress.com/downregulation-of-b-cell-lymphomaleukemia-2-by-overexpressed-microrna--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wenlin Bai,1,2,* Yujiao Chen,1,2,* Pengling Sun,1,2 Ai Gao1,2 1Department of Occupational Health and Environmental Health, School of Public Health, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells. Keywords: titanium dioxide nanoparticles, autophagy, miR34a, Bcl-2, lentivirus, cell death, cytotoxicityBai WChen YSun PGao ADove Medical PressarticleTitanium dioxide nanoparticlesautophagymiR34aBcl-2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1959-1971 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Titanium dioxide nanoparticles autophagy miR34a Bcl-2 Medicine (General) R5-920
spellingShingle	Titanium dioxide nanoparticles autophagy miR34a Bcl-2 Medicine (General) R5-920 Bai W Chen Y Sun P Gao A Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
description	Wenlin Bai,1,2,* Yujiao Chen,1,2,* Pengling Sun,1,2 Ai Gao1,2 1Department of Occupational Health and Environmental Health, School of Public Health, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells. Keywords: titanium dioxide nanoparticles, autophagy, miR34a, Bcl-2, lentivirus, cell death, cytotoxicity
format	article
author	Bai W Chen Y Sun P Gao A
author_facet	Bai W Chen Y Sun P Gao A
author_sort	Bai W
title	Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
title_short	Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
title_full	Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
title_fullStr	Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
title_full_unstemmed	Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells
title_sort	downregulation of b-cell lymphoma/leukemia-2 by overexpressed microrna 34a enhanced titanium dioxide nanoparticle-induced autophagy in beas-2b cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/a9b178ab36984be9aa94da034a9a08a8
work_keys_str_mv	AT baiw downregulationofbcelllymphomaleukemia2byoverexpressedmicrorna34aenhancedtitaniumdioxidenanoparticleinducedautophagyinbeas2bcells AT cheny downregulationofbcelllymphomaleukemia2byoverexpressedmicrorna34aenhancedtitaniumdioxidenanoparticleinducedautophagyinbeas2bcells AT sunp downregulationofbcelllymphomaleukemia2byoverexpressedmicrorna34aenhancedtitaniumdioxidenanoparticleinducedautophagyinbeas2bcells AT gaoa downregulationofbcelllymphomaleukemia2byoverexpressedmicrorna34aenhancedtitaniumdioxidenanoparticleinducedautophagyinbeas2bcells
_version_	1718399531779883008

Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

Ejemplares similares