Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research,...

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Autores principales: Qin X, Yu S, Zhou L, Shi M, Hu Y, Xu X, Shen B, Liu S, Yan D, Feng J
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:b87c439ee55d4665a8a92b32cb32662d2021-12-02T02:10:25ZCisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner1178-2013https://doaj.org/article/b87c439ee55d4665a8a92b32cb32662d2017-05-01T00:00:00Zhttps://www.dovepress.com/cisplatin-resistant-lung-cancer-cell-derived-exosomes-increase-cisplat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer. Keywords: lung cancer, cisplatin, exosome, miR-100–5p, drug resistanceQin XYu SZhou LShi MHu YXu XShen BLiu SYan DFeng JDove Medical Pressarticlelung cancercisplatinexosomemiR-100-5pMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3721-3733 (2017)
institution DOAJ
collection DOAJ
language EN
topic lung cancer
cisplatin
exosome
miR-100-5p
Medicine (General)
R5-920
spellingShingle lung cancer
cisplatin
exosome
miR-100-5p
Medicine (General)
R5-920
Qin X
Yu S
Zhou L
Shi M
Hu Y
Xu X
Shen B
Liu S
Yan D
Feng J
Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
description Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer. Keywords: lung cancer, cisplatin, exosome, miR-100–5p, drug resistance
format article
author Qin X
Yu S
Zhou L
Shi M
Hu Y
Xu X
Shen B
Liu S
Yan D
Feng J
author_facet Qin X
Yu S
Zhou L
Shi M
Hu Y
Xu X
Shen B
Liu S
Yan D
Feng J
author_sort Qin X
title Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
title_short Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
title_full Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
title_fullStr Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
title_full_unstemmed Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner
title_sort cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal mir-100–5p-dependent manner
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/b87c439ee55d4665a8a92b32cb32662d
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