MiR-1246b, a novel miRNA molecule of extracellular vesicles in bronchoalveolar lavage fluid promotes the nodules growth through FGF14 in patients with lung cancers

Abstract

Abstract With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has been increasing, therefore, the judgment of benign and malignant nodules has become a common problem in clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients, BALF was obtained and EVs were isolated, and small RNA sequencing was performed to screen differential miRNAs between benign and malignant pulmonary nodules groups. The binding targets and underlying mechanisms of the differential miRNAs were verified by in vitro and in vivo experiments. EVs were successfully isolated and identified after obtaining BALF by R-EBUS localization. Differential miRNAs in BALF-EVs of patients with benign or malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new sequence, miR-1246b, was noticed. We found that FGF14 was the binding target of miR-1246b by luciferase Assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further led to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist to distinguish malignant nodules from benign nodules. miR-1246b, extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.