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.
Highlights
Lung cancer, one of the most common cancers worldwide, leads to high cancer-related death among both men and women (Siegel et al, 2019)
We found that the levels of miR-92b-3p in plasma exosomes were significantly increased in small cell lung cancer (SCLC) patients with chemoresistance compared with patients without chemoresistance
Our study reveals novel details elaborating the molecular mechanism of exosomal miR-92b-3p in SCLC chemoresistance and offers theoretical basis for identifying effective targets to improve the prognosis of SCLC chemoresistant patients
Summary
One of the most common cancers worldwide, leads to high cancer-related death among both men and women (Siegel et al, 2019). The first line of treatment regimen for SCLC is platinum-based chemotherapy, usually in combination with the topoisomerase II inhibitor etoposide (William and Glisson, 2011; Borromeo et al, 2016). The treatment regimen shows a good initial response in 60–80% SCLC patients, but almost all patients relapse within 6–12 months of treatment due to the development of multidrug resistance (MDR; Peng et al, 2016). The indicators currently used for monitoring SCLC chemoresistance are imaging data and traditional tumor markers, such as carcinoembryonic antigen, pro-gastrin-releasing peptide, and neuron-specific enolase. Most traditional tumor markers lack high sensitivity and specificity. It is urgent to find reliable predictors and elucidate the molecular mechanism of SCLC chemoresistance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
