Exosomal circPOLK promotes metastasis of NSCLC cells via regulating mir-1204/SOX8 axis
摘要
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and the prognosis of NSCLC patients is still poor particularly for patients with metastatic disease. Thus, extending the knowledge about the mechanism of metastasis is critical for NSCLC treatment. We demonstrated that hsa_circ_0073052 (circPOLK) was overexpressed in blood exosomes from cancer patients than those from healthy people. CircPOLK overexpression enhanced the metastasis and EMT progression of NSCLC cells. Next, circPOLK might function as miRNA sponge in NSCLC cells. Through bioinformatical prediction and RNA pull-down experiment, miR-1204 might be a potential target of circPOLK. Interestingly, serumal miR-1204 was an efficacious diagnostic and prognostic molecular for lung cancer patients and acted as a suppressor on NSCLC progression. Furthermore, circPOLK promoted metastasis of NSCLC via regulating miR-1204. Furthermore, SOX8 was identified as a potential target of circPOLK/miR-1204. GO enrichment of circPOLK regulated DEGs showed that circPOLK might be involved in angiogenesis of NSCLC. Indeed, circPOLK secreted by NSCLC cells could promote angiogenesis. Our dada not only identifies a novel circPOLK/miR-1204/SOX8 signaling pathway, but also provides therapeutical strategies for NSCLC patients with metastatic disease.
Graphical abstract