Circ_CIT Promotes Nasopharyngeal Carcinoma Progression and Macrophage M2 Polarization Through miR-409-3p/ZEB1 Axis.

PURPOSE: Circular RNAs (circRNAs) play a crucial role in the progression of various cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism of circRNA in the progression of NPC remains to be elucidated. PATIENTS AND METHODS: The expression levels of circ_CIT, microRNA-409-3p and ZEB1 in NPC tissues were detected by Real-time quantitative PCR (qRT-PCR). Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ_CIT. Dual luciferase reporter was performed to confirm the binding of circ_CIT with micro (miR)-409-3p. Cellular behaviors were determined using Cell Counting Kit-8 (CCK-8), colony formation, wound healing, transwell and macrophage chemotaxis assays. Enzyme Linked Immunosorbent Assay (ELISA) and immunofluorescence Assays was used to evaluated macrophage markers. RESULTS: We identified that circ_CIT was mainly located in the cytoplasm. Circ_CIT expression was increased in NPC tissues and cell lines. Knockdown of circ_CIT inhibited cell proliferation, invasion and migration. Circ_CIT-mediated NPC tumorigenesis by sponging miR-409-3p and promoting ZEB1 expression. The inhibitors of miR-409-3p could reverse the effects of circ_CIT knockdown on NPC cells. The expression of circ_CIT and ZEB1 was found to be positively correlated with NPC tumor stage. Downregulation of expression of circ_CIT could promote macrophage M2 polarization through NPC cells. Overexpression of ZEB1 could reverse the inhibitory effect of circ_CIT knockdown on the polarization of macrophages to M2 phenotype. CONCLUSION: Highly expressed circ_CIT adsorbs miR-409-3p to upregulate ZEB1 expression, thereby promoting the proliferation and metastatic ability of NPC cells and activating macrophage M2 polarization. Therefore, circ_CIT may be a potential therapeutic target for NPC patients.