期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.661602
关键词
exosome; miR-92b-3p; small cell lung cancer; chemoresistance; migration
资金
- Natural Science Foundation of Anhui Province [2008085MH288]
- National Natural Science Foundation of China [81972191]
- Science and Technology Major Project of Anhui Province [18030801140]
- Fundamental Research Funds for Central University [WK9110000025, WK9110000072, WK9110000071]
- National Cancer Center Climbing Funds [NCC201812B036]
- High Magnetic Field Laboratory of Anhui Province
The study revealed that miR-92b-3p expression was increased in SCLC patients and correlated with chemoresistance. By affecting the PTEN/AKT regulatory network, miR-92b-3p mediated cell migration and chemoresistance in SCLC. Additionally, miR-92b-3p was identified as a potential dynamic biomarker for monitoring chemoresistance in SCLC.
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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