LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells

Abstract Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJ...

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Autores principales:	Youguang Pu, Yiao Tan, Chunbao Zang, Fangfang Zhao, Cifeng Cai, Lingsuo Kong, Hui Deng, Fengmei Chao, Ran Xia, Minghua Xie, Fangfang Ge, Yueyin Pan, Shanbao Cai, Dabing Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/b0492a48926b4bffa3f4d12033f6c756
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spelling	oai:doaj.org-article:b0492a48926b4bffa3f4d12033f6c7562021-12-05T12:04:27ZLAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells10.1038/s41419-021-04413-02041-4889https://doaj.org/article/b0492a48926b4bffa3f4d12033f6c7562021-12-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04413-0https://doaj.org/toc/2041-4889Abstract Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.Youguang PuYiao TanChunbao ZangFangfang ZhaoCifeng CaiLingsuo KongHui DengFengmei ChaoRan XiaMinghua XieFangfang GeYueyin PanShanbao CaiDabing HuangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Youguang Pu Yiao Tan Chunbao Zang Fangfang Zhao Cifeng Cai Lingsuo Kong Hui Deng Fengmei Chao Ran Xia Minghua Xie Fangfang Ge Yueyin Pan Shanbao Cai Dabing Huang LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
description	Abstract Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.
format	article
author	Youguang Pu Yiao Tan Chunbao Zang Fangfang Zhao Cifeng Cai Lingsuo Kong Hui Deng Fengmei Chao Ran Xia Minghua Xie Fangfang Ge Yueyin Pan Shanbao Cai Dabing Huang
author_facet	Youguang Pu Yiao Tan Chunbao Zang Fangfang Zhao Cifeng Cai Lingsuo Kong Hui Deng Fengmei Chao Ran Xia Minghua Xie Fangfang Ge Yueyin Pan Shanbao Cai Dabing Huang
author_sort	Youguang Pu
title	LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
title_short	LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
title_full	LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
title_fullStr	LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
title_full_unstemmed	LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells
title_sort	lamtor5-as1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of nrf2 in osteosarcoma cells
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/b0492a48926b4bffa3f4d12033f6c756
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LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells

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