MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression

Cadmium is an environmental pollutant that threatens the health of both humans and animals. Current studies have shown that while hepatotoxic damage induced by cadmium is closely related to autophagy, its intrinsic mechanism has not been elucidated. MicroRNA plays a regulatory role on different stag...

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Autores principales:	Hui Zou, Ling Wang, Jianya Zhao, Yan Yuan, Tao Wang, Jianchun Bian, Zongping Liu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cadmium MiR-155 Rheb Autophagy Hepatocytes Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/32078b6f4a8045e1b40fc5133acb7c9b
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spelling	oai:doaj.org-article:32078b6f4a8045e1b40fc5133acb7c9b2021-11-06T04:15:39ZMiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression0147-651310.1016/j.ecoenv.2021.112895https://doaj.org/article/32078b6f4a8045e1b40fc5133acb7c9b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321010071https://doaj.org/toc/0147-6513Cadmium is an environmental pollutant that threatens the health of both humans and animals. Current studies have shown that while hepatotoxic damage induced by cadmium is closely related to autophagy, its intrinsic mechanism has not been elucidated. MicroRNA plays a regulatory role on different stages of autophagy. In this study, we investigated the mechanisms by which microRNA-155 (miR-155) regulate cadmium-induced hepatotoxicity in rat hepatocytes (BRL 3A cells) and in vivo. We found that cadmium exposure could cause liver injury in rats, resulting in a decreased liver index, increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity, hepatocyte steatosis, and ultrastructure damage. Cadmium exposure also induced autophagy in hepatocytes, resulting in increased expression of ATG5, Belin1, LC3II, and an increased number of autophagosomes. In addition, cadmium exposure upregulated miR-155 expression, downregulated Rheb mRNA expression, and downregulated the level of protein expression in the Rheb/mTOR signaling pathway in rat hepatocytes. The overexpression of miR-155 followed by cadmium exposure upregulated the level of autophagy in BRL3A cells, whereas miR-155 inhibition had the opposite effect. In addition, miR-155 negatively regulated Rheb. A dual-luciferase reporter assay verified the negative regulatory effect of miR-155 on Rheb targeting. Knockdown of Rheb downregulated cadmium-induced autophagy. Therefore, the Rheb/mTOR signaling can negatively regulate autophagy. The present study demonstrates that miR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression.Hui ZouLing WangJianya ZhaoYan YuanTao WangJianchun BianZongping LiuElsevierarticleCadmiumMiR-155RhebAutophagyHepatocytesEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112895- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cadmium MiR-155 Rheb Autophagy Hepatocytes Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Cadmium MiR-155 Rheb Autophagy Hepatocytes Environmental pollution TD172-193.5 Environmental sciences GE1-350 Hui Zou Ling Wang Jianya Zhao Yan Yuan Tao Wang Jianchun Bian Zongping Liu MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
description	Cadmium is an environmental pollutant that threatens the health of both humans and animals. Current studies have shown that while hepatotoxic damage induced by cadmium is closely related to autophagy, its intrinsic mechanism has not been elucidated. MicroRNA plays a regulatory role on different stages of autophagy. In this study, we investigated the mechanisms by which microRNA-155 (miR-155) regulate cadmium-induced hepatotoxicity in rat hepatocytes (BRL 3A cells) and in vivo. We found that cadmium exposure could cause liver injury in rats, resulting in a decreased liver index, increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity, hepatocyte steatosis, and ultrastructure damage. Cadmium exposure also induced autophagy in hepatocytes, resulting in increased expression of ATG5, Belin1, LC3II, and an increased number of autophagosomes. In addition, cadmium exposure upregulated miR-155 expression, downregulated Rheb mRNA expression, and downregulated the level of protein expression in the Rheb/mTOR signaling pathway in rat hepatocytes. The overexpression of miR-155 followed by cadmium exposure upregulated the level of autophagy in BRL3A cells, whereas miR-155 inhibition had the opposite effect. In addition, miR-155 negatively regulated Rheb. A dual-luciferase reporter assay verified the negative regulatory effect of miR-155 on Rheb targeting. Knockdown of Rheb downregulated cadmium-induced autophagy. Therefore, the Rheb/mTOR signaling can negatively regulate autophagy. The present study demonstrates that miR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression.
format	article
author	Hui Zou Ling Wang Jianya Zhao Yan Yuan Tao Wang Jianchun Bian Zongping Liu
author_facet	Hui Zou Ling Wang Jianya Zhao Yan Yuan Tao Wang Jianchun Bian Zongping Liu
author_sort	Hui Zou
title	MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
title_short	MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
title_full	MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
title_fullStr	MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
title_full_unstemmed	MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression
title_sort	mir-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing rheb expression
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/32078b6f4a8045e1b40fc5133acb7c9b
work_keys_str_mv	AT huizou mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT lingwang mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT jianyazhao mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT yanyuan mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT taowang mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT jianchunbian mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression AT zongpingliu mir155promotescadmiuminducedautophagyinrathepatocytesbysuppressingrhebexpression
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MiR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression

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