Extracellular vesicle-delivered miR-505-5p, as a diagnostic biomarker of early lung adenocarcinoma, inhibits cell apoptosis by targeting TP53AIP1

Abstract

Lung adenocarcinoma (LA) is the most commonly occurring histological type of non-small cell lung cancer. Diagnosis and treatment of LA remain a major clinical challenge. In the present study, to identify early LA biomarkers, extracellular vesicles (EVs) were separated from the plasma samples from 153 patients with LA and 75 healthy controls. microRNA (miRNA) expression profiling was performed at the screening stage (5 patients with LA vs. 5 controls), followed by verification at the validation stage (40 patients with LA vs. 20 controls) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The four disordered miRNAs (miR-505-5p, miR-486-3p, miR-486-3p and miR-382-3p) identified in the plasma EVs were further evaluated at the testing stage (108 patients with LA vs. 50 controls) by RT-qPCR. It was revealed that miR-505-5p was upregulated, whereas miR-382-3p was downregulated, in the EVs from patients with LA. Furthermore, miR-505-5p was also upregulated in tumor tissues, compared with adjacent non-tumor control tissues. Subsequently, the direct targets of miR-505-5p were predicted using bioinformatics analyses, and verified by luciferase assay and immunoblotting. The present study determined that miR-505-5p functions as an oncogene, promoting lung cancer cell proliferation and inhibiting cancer cell apoptosis via the targeting of tumor protein P53-regulated apoptosis-inducing protein 1 (TP53AIP1). Finally, it was confirmed that miR-505-5p in plasma EVs could be delivered to lung cancer cells, inhibiting cell apoptosis and promoting cell proliferation by targeting TP53AIP1. In conclusion, the present study indicated that miRNA-505-5p functions as an oncogene that may be used as a novel biomarker for the diagnosis and treatment of LA.