LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mech...

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Autores principales:	Wen-Su Wei, Ning Wang, Min-hua Deng, Pei Dong, Jian-ye Liu, Zhen Xiang, Xiang-Dong Li, Zhi-yong Li, Zhen-hua Liu, Yu-lu Peng, Zhen Li, Li-Juan Jiang, Kai Yao, Yun-lin Ye, Wen-hua Lu, Zhi-Ling Zhang, Fang-Jian Zhou, Zhuo-Wei Liu, Dan Xie, Chun-ping Yu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Urothelial carcinoma of the bladder LRPPRC circRNA FOXM1 ROS Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/71b4bfd3811c4c2c8cef0c6e2fea7100
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spelling	oai:doaj.org-article:71b4bfd3811c4c2c8cef0c6e2fea71002021-12-04T04:34:04ZLRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis2213-231710.1016/j.redox.2021.102201https://doaj.org/article/71b4bfd3811c4c2c8cef0c6e2fea71002021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S221323172100361Xhttps://doaj.org/toc/2213-2317Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.Wen-Su WeiNing WangMin-hua DengPei DongJian-ye LiuZhen XiangXiang-Dong LiZhi-yong LiZhen-hua LiuYu-lu PengZhen LiLi-Juan JiangKai YaoYun-lin YeWen-hua LuZhi-Ling ZhangFang-Jian ZhouZhuo-Wei LiuDan XieChun-ping YuElsevierarticleUrothelial carcinoma of the bladderLRPPRCcircRNAFOXM1ROSMedicine (General)R5-920Biology (General)QH301-705.5ENRedox Biology, Vol 48, Iss , Pp 102201- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Urothelial carcinoma of the bladder LRPPRC circRNA FOXM1 ROS Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Urothelial carcinoma of the bladder LRPPRC circRNA FOXM1 ROS Medicine (General) R5-920 Biology (General) QH301-705.5 Wen-Su Wei Ning Wang Min-hua Deng Pei Dong Jian-ye Liu Zhen Xiang Xiang-Dong Li Zhi-yong Li Zhen-hua Liu Yu-lu Peng Zhen Li Li-Juan Jiang Kai Yao Yun-lin Ye Wen-hua Lu Zhi-Ling Zhang Fang-Jian Zhou Zhuo-Wei Liu Dan Xie Chun-ping Yu LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
description	Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.
format	article
author	Wen-Su Wei Ning Wang Min-hua Deng Pei Dong Jian-ye Liu Zhen Xiang Xiang-Dong Li Zhi-yong Li Zhen-hua Liu Yu-lu Peng Zhen Li Li-Juan Jiang Kai Yao Yun-lin Ye Wen-hua Lu Zhi-Ling Zhang Fang-Jian Zhou Zhuo-Wei Liu Dan Xie Chun-ping Yu
author_facet	Wen-Su Wei Ning Wang Min-hua Deng Pei Dong Jian-ye Liu Zhen Xiang Xiang-Dong Li Zhi-yong Li Zhen-hua Liu Yu-lu Peng Zhen Li Li-Juan Jiang Kai Yao Yun-lin Ye Wen-hua Lu Zhi-Ling Zhang Fang-Jian Zhou Zhuo-Wei Liu Dan Xie Chun-ping Yu
author_sort	Wen-Su Wei
title	LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
title_short	LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
title_full	LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
title_fullStr	LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
title_full_unstemmed	LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis
title_sort	lrpprc regulates redox homeostasis via the circankhd1/foxm1 axis to enhance bladder urothelial carcinoma tumorigenesis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/71b4bfd3811c4c2c8cef0c6e2fea7100
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LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

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