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

Abstract

With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a common problem in the 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, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. 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 leading 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 in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.