Institution: | 1. Department of Thoracic Surgery, JiangxiCancer Hospital, Nanchang, China
Contribution: Conceptualization (equal), Funding acquisition (equal), Writing - original draft (equal);2. Department of Thoracic Surgery, JiangxiCancer Hospital, Nanchang, China
Contribution: Data curation (equal), Resources (equal);3. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Contribution: Formal analysis (equal), Methodology (equal);4. Department of Thoracic Surgery, JiangxiCancer Hospital, Nanchang, China
Contribution: Project administration (equal), Validation (equal);5. Department of Thoracic Surgery, JiangxiCancer Hospital, Nanchang, China
Contribution: Software (equal), Visualization (equal);6. Department of Thoracic Surgery, JiangxiCancer Hospital, Nanchang, China
Contribution: Conceptualization (equal), Supervision (equal);7. Department of Breast Surgery, JiangxiCancer Hospital, Nanchang, China |
Abstract: | Lung cancer is the most aggressive tumour afflicting patients on a global scale. Extracellular vesicle (EV)-delivered microRNAs (miRs) have been reported to play critical roles in cancer development. The current study aimed to investigate the role of hypoxic bone marrow mesenchymal cell (BMSC)-derived EVs containing miR-328-3p in lung cancer. miR-328-3p expression was determined in a set of lung cancer tissues by RT-qPCR. BMSCs were infected with lentivirus-mediated miR-328-3p knock-down and then cultured in normoxic or hypoxic conditions, followed by isolation of EVs. Following ectopic expression and depletion experiments in lung cancer cells, the biological functions of miR-328-3p were analysed using CCK-8 assay, flow cytometry and Transwell assay. Xenograft in nude mice was performed to test the in vivo effects of miR-328-3p delivered by hypoxic BMSC-derived EVs on tumour growth of lung cancer. Finally, the expression of circulating miR-328-3p was detected in the serum of lung cancer patients. miR-328-3p was highly expressed in EVs derived from hypoxic BMSCs. miR-328-3p was delivered to lung cancer cells by hypoxic BMSC-derived EVs, thereby promoting lung cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition. miR-328-3p targeted NF2 to inactivate the Hippo pathway. Moreover, EV-delivered miR-328-3p increased tumour growth in vivo. Additionally, circulating miR-328-3p was bioactive in the serum of lung cancer patients. Taken together, our results demonstrated that hypoxic BMSC-derived EVs could deliver miR-328-3p to lung cancer cells and that miR-328-3p targets the NF2 gene, thereby inhibiting the Hippo pathway to ultimately promote the occurrence and progression of lung cancer. |