Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells

Abstract Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing...

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Autores principales:	Zhengpei Zhang, Ling Yu, Guo Dai, Kezhou Xia, Gaiwei Liu, Qi Song, Chunjie Tao, Tian Gao, Weichun Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b900072c2a1a4c12a1d73abcb8c2bbea
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spelling	oai:doaj.org-article:b900072c2a1a4c12a1d73abcb8c2bbea2021-12-02T11:40:21ZTelomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells10.1038/s41598-017-07204-w2045-2322https://doaj.org/article/b900072c2a1a4c12a1d73abcb8c2bbea2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07204-whttps://doaj.org/toc/2045-2322Abstract Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells. In this study, confocal fluorescence microscopy experiments revealed that TERT translocates from the nucleus to mitochondria in cisplatin treated osteosarcoma cells. We observed decreased apoptosis rate and improved mitochondrial function in TERT-overexpressing cells following cisplatin treatment. Based on these results, we further established that TERT inhibits cisplatin-induced apoptosis independently of telomerase reverse transcriptase activity. Moreover, TERT suppressed cisplatin-induced apoptosis and improved mitochondrial function via alleviating intracellular ROS in osteosarcoma cells. Our finding that TERT shuttles from the nucleus to the mitochondrion in response to cisplatin treatment and inhibits cisplatin-induced apoptosis in osteosarcoma cells may be especially important to overcome drug resistance.Zhengpei ZhangLing YuGuo DaiKezhou XiaGaiwei LiuQi SongChunjie TaoTian GaoWeichun GuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhengpei Zhang Ling Yu Guo Dai Kezhou Xia Gaiwei Liu Qi Song Chunjie Tao Tian Gao Weichun Guo Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
description	Abstract Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells. In this study, confocal fluorescence microscopy experiments revealed that TERT translocates from the nucleus to mitochondria in cisplatin treated osteosarcoma cells. We observed decreased apoptosis rate and improved mitochondrial function in TERT-overexpressing cells following cisplatin treatment. Based on these results, we further established that TERT inhibits cisplatin-induced apoptosis independently of telomerase reverse transcriptase activity. Moreover, TERT suppressed cisplatin-induced apoptosis and improved mitochondrial function via alleviating intracellular ROS in osteosarcoma cells. Our finding that TERT shuttles from the nucleus to the mitochondrion in response to cisplatin treatment and inhibits cisplatin-induced apoptosis in osteosarcoma cells may be especially important to overcome drug resistance.
format	article
author	Zhengpei Zhang Ling Yu Guo Dai Kezhou Xia Gaiwei Liu Qi Song Chunjie Tao Tian Gao Weichun Guo
author_facet	Zhengpei Zhang Ling Yu Guo Dai Kezhou Xia Gaiwei Liu Qi Song Chunjie Tao Tian Gao Weichun Guo
author_sort	Zhengpei Zhang
title	Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
title_short	Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
title_full	Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
title_fullStr	Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
title_full_unstemmed	Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
title_sort	telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b900072c2a1a4c12a1d73abcb8c2bbea
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Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells

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