Exosomal circPOLK promotes metastasis of NSCLC cells via regulating mir-1204/SOX8 axis

Abstract 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. Furthermore, circPOLK was identified as a circular RNA and generated from host gene POLK by back-splicing in NSCLC cells. Although circPOLK knockdown could not affect the proliferation of NSCLC cells, circPOLK overexpression enhanced the migration/invasion and EMT progression of NSCLC cells in vitro. In vivo, NSCLC transfected with shcircPOLK exhibited less metastatic foci in nude mice as compared to those transfected with empty vector. Next, we found that 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 NSCLC suppressor on cancer progression. Furthermore, circPOLK promoted metastasis of NSCLC via regulating miR-1204. To further identify the potential target mRNA of circPOLK/miR-1204, a Venn diagram was generated showing that there were eight overlapping genes among circPOLK regulated differentially expressed genes (DEGs) and potential downstream targets of miR-1204 by bioinformatical predictions. 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.