Abstract
Exosomes play critical roles in regulating various physiological and pathological processes, including immune stimulation, immune suppression, cardiovascular diseases, and cancers. Recent studies show that exosomes that transport specific microRNAs (miRNAs) are involved in tumor development. However, the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer (NSCLC) is not well understood. Here, we show that exosomes shuttling low levels of miR-34c-3p are involved in NSCLC progression. Our results showed that exosomes derived from NSCLC cells carrying low levels of miR-34c-3p could be transported into the cytoplasm of NSCLC cells and accelerate NSCLC invasion and migration by upregulating integrin α2β1. A luciferase assay revealed that integrin α2β1 was the direct target of miR-34c-3p, and overexpression of integrin α2β1 could promote the invasion and migration of NSCLC cells. The analysis of exosomes derived from clinical serum samples indicated that the expression of miR-34c-3p was significantly downregulated in exosomes from NSCLC patients compared with that of normal controls. A549-derived exosomes promoted NSCLC cells lung metastases in vivo. Exosomes shuttling low levels of miR-34c-3p were associated with the progression of NSCLC in vitro and in vivo. Our data demonstrate that exosomes shuttling low levels of miR-34c-3p can accelerate the invasion and migration of NSCLC by upregulating integrin α2β1. MiR-34c-3p can be a diagnostic and prognostic marker for NSCLC. High expression of integrin α2β1 is positively related to the migration and metastasis of NSCLC cells.
Highlights
It is known that lung cancer plays is responsible for a large number of cancer-related deaths worldwide.[1]
We found that exosomes derived from nonsmall cell lung cancer (NSCLC) cells were round vesicles that ranged from 30 to 120 nm in size (Fig. 1a)
The exosome preparation was confirmed to contain round vesicles measuring 30–120 nm in diameter by electron microscopy (Fig. 1d). These results indicated that the exosomes isolated from NSCLC cells were sufficiently pure for subsequent experiments
Summary
It is known that lung cancer plays is responsible for a large number of cancer-related deaths worldwide.[1] there have been great improvements in both diagnosis and treatment, the mortality of lung cancer remains high. The 5-year survival of lung cancer is below 15%.2. Lung cancer is usually classified as nonsmall cell lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC is more common, and it more metastasizes.[3]. Understanding the molecular mechanisms involved in the development of NSCLC will help in prognosis and in the development of novel therapeutic targets.[4]
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.
