Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway

Objective: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. Results: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p’s effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. Conclusion: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.