Circular RNA Hsa_circ_0066755 as an Oncogene via sponging miR-651 and as a Promising Diagnostic Biomarker for Nasopharyngeal Carcinoma

Background: Circular RNAs (circRNAs) represent a class of broad and diversified endogenous RNAs that regulate gene expressions in eukaryotes. Hsa_circ_006675 has been proven as an important circRNA molecule in nasopharyngeal carcinoma (NPC), however, its function still remains elusive. This study aims to discuss the biofunctions of hsa_circ_0066755 in NPC. Methods: We detected the expression levels of hsa_circ_0066755 in NPC patients by quantitative real-time polymerase chain reaction (qRT-PCR), and the corresponding ROC curves were plotted. Functional experiments including CCK-8, colony formation, Transwell assay and Xenograft experiment were conducted. Bioinformatics analysis was performed to seek miRNAs which might have binding sites with hsa_circ_0066755. Luciferase reporter assays were finally carried out to verify the binding sites. Results: We found significant increases of hsa_circ_0066755 in the plasma and tissues of the patients. Moreover, its levels were positively correlated with clinical staging (P=0.019). The receiver operating characteristic (ROC) analysis showed that the area under the curves (AUCs) of tissue and plasma hsa_circ_0066755 for distinguishing NPC from non-cancerous controls were 0.8537 and 0.9044, respectively. Both tissue and plasma hsa_circ_0066755 testing presented a comparable diagnostic accuracy to the magnetic resonance imaging (MRI). Our in-vitro experiment showed that the overexpression of hsa_circ_0066755 facilitated the growth, proliferation, clone formation, invasion and migration of CNE-1 NPC cells, while its down-regulation showed completely opposite effects. The xenograft experiment showed that exogenous hsa_circ_0066755 could significantly enhance the in-vivo tumorigenic ability of CNE-1 cells. Rescue assay further confirmed hsa_circ_0066755 as a tumor facilitator by sponging miR-651. Conclusions: Collectively, this study reported for the first time that hsa_circ_0066755 played a role of oncogene in NPC and could be used as an effective diagnostic marker for NPC, and that hsa_circ_0066755 / miR-651 axis also involved in the progression of NPC.