Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783707868249194496 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8201786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liming exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT shanwulin exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT huayan exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT chaofengmei exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT cuiyayun exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT lvlei exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT douxiaoyan exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT bianxing exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT zoujinglu exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT lihong exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway AT linwenchu exosomalmir92b3ppromoteschemoresistanceofsmallcelllungcancerthroughtheptenaktpathway |