Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 11; pp. 6324 - 6339
• Main Authors: Wang, Li, He, Jun, Hu, Haoyue, Tu, Li, Sun, Zhen, Liu, Yanyang, Luo, Feng
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2020; John Wiley and Sons Inc
• Subjects: Antibodies; Base Sequence; Bioinformatics; Biosynthesis; Biotechnology; Cell culture; Cell interactions; Cell Line, Tumor; Endocytosis; exosome; Exosomes; Exosomes - metabolism; Exosomes - ultrastructure; Fibroblast growth factors; Gene Expression Regulation, Neoplastic; Gene Silencing; Genotype & phenotype; Growth factors; Humans; Lung cancer; lung cancer stem cell; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Membrane vesicles; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐210‐3p; Neoplastic Stem Cells - metabolism; Original; Phenotype; Phenotypes; Proteins; Receptor, Fibroblast Growth Factor, Type 5 - metabolism; Spheres; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Stem cells; Therapeutic applications; Tumor microenvironment; Tumors; Vimentin; Beijing China; China; lung cancer stem cell; miR-210-3p; metastasis; exosome
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15274

Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC‐derived exosomes promote the migration and invasion of lung cancer cells, up‐regulate expression levels of N‐cadherin, vimentin, MMP‐9 and MMP‐1, and down‐regulate E‐cadherin expression. Moreover, we verified that these exosomes contribute to a pro‐metastatic phenotype in lung cancer cells via miR‐210‐3p transfer. The results of bioinformatics analysis and dual‐luciferase reporter assays further indicated that miR‐210‐3p may bind to fibroblast growth factor receptor‐like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC‐derived exosomal miR‐210‐3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.