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

Authors :
Ming Li
Wulin Shan
Yan Hua
Fengmei Chao
Yayun Cui
Lei Lv
Xiaoyan Dou
Xing Bian
Jinglu Zou
Hong Li
Wenchu Lin
Source :
Frontiers in Cell and Developmental Biology, Frontiers in Cell and Developmental Biology, Vol 9 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

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.

Details

Language :
English
ISSN :
2296634X
Volume :
9
Database :
OpenAIRE
Journal :
Frontiers in Cell and Developmental Biology
Accession number :
edsair.doi.dedup.....045cd2ebd0c7287afb1b7a845fafad7a