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

• Published in: Frontiers in cell and developmental biology Vol. 9; p. 661602
• Main Authors: Li, Ming, Shan, Wulin, Hua, Yan, Chao, Fengmei, Cui, Yayun, Lv, Lei, Dou, Xiaoyan, Bian, Xing, Zou, Jinglu, Li, Hong, Lin, Wenchu
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 31-05-2021
• Subjects: Cell and Developmental Biology; chemoresistance; exosome; migration; miR-92b-3p; small cell lung cancer
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.661602

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.