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Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway

Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never be...

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Autores principales: Li, Ming, Shan, Wulin, Hua, Yan, Chao, Fengmei, Cui, Yayun, Lv, Lei, Dou, Xiaoyan, Bian, Xing, Zou, Jinglu, Li, Hong, Lin, Wenchu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201786/
https://www.ncbi.nlm.nih.gov/pubmed/34136482
http://dx.doi.org/10.3389/fcell.2021.661602
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author Li, Ming
Shan, Wulin
Hua, Yan
Chao, Fengmei
Cui, Yayun
Lv, Lei
Dou, Xiaoyan
Bian, Xing
Zou, Jinglu
Li, Hong
Lin, Wenchu
author_facet Li, Ming
Shan, Wulin
Hua, Yan
Chao, Fengmei
Cui, Yayun
Lv, Lei
Dou, Xiaoyan
Bian, Xing
Zou, Jinglu
Li, Hong
Lin, Wenchu
author_sort Li, Ming
collection PubMed
description Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.
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spelling pubmed-82017862021-06-15 Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway Li, Ming Shan, Wulin Hua, Yan Chao, Fengmei Cui, Yayun Lv, Lei Dou, Xiaoyan Bian, Xing Zou, Jinglu Li, Hong Lin, Wenchu Front Cell Dev Biol Cell and Developmental Biology Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC. Frontiers Media S.A. 2021-05-31 /pmc/articles/PMC8201786/ /pubmed/34136482 http://dx.doi.org/10.3389/fcell.2021.661602 Text en Copyright © 2021 Li, Shan, Hua, Chao, Cui, Lv, Dou, Bian, Zou, Li and Lin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Li, Ming
Shan, Wulin
Hua, Yan
Chao, Fengmei
Cui, Yayun
Lv, Lei
Dou, Xiaoyan
Bian, Xing
Zou, Jinglu
Li, Hong
Lin, Wenchu
Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title_full Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title_fullStr Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title_full_unstemmed Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title_short Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
title_sort exosomal mir-92b-3p promotes chemoresistance of small cell lung cancer through the pten/akt pathway
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201786/
https://www.ncbi.nlm.nih.gov/pubmed/34136482
http://dx.doi.org/10.3389/fcell.2021.661602
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