Long Noncoding RNA CCDC26 Promotes Thyroid Cancer Malignant Progression via miR-422a/EZH2/Sirt6 Axis

Purpose: Long noncoding RNAs are crucial regulators in thyroid cancer progression. However, the role of lncRNA CCDC26 in thyroid cancer remains unclear. Here, we aimed to explore the effect of CCDC26 on thyroid cancer progression and the underlying mechanism. Materials and Methods: A total of 50 clinical thyroid cancer samples were studied in patients' samples, cultured cells, and nude mice before and after treatment using quantitative reverse transcription-PCR, CCK-8 assays, BrdU incorporation assays, Transwell assays, cell apoptosis analysis, luciferase reporter gene assay, RNA immunoprecipitation, Western blot analysis, and tumorigenicity analysis. Results: CCDC26 expression was elevated in patients' thyroid cancer tissues and thyroid cancer cell lines. CCDC26 depletion remarkably reduced proliferation, invasion, and migration but induced apoptosis of thyroid cancer cells. Mechanically, miR-422a mimic remarkably reduced the luciferase activity of CCDC26 transfected cells but failed to affect cells transfected with CCDC26 containing the mutated miR-422a-binding site. RNA immunoprecipitation (RIP) assays showed that CCDC26 and miR-422a preferentially interacted with Ago2, but not IgG, in the micro-ribonucleoprotein complexes (miRNPs). CCDC26 depletion enhanced miR-422a expression and MiR-422a inhibitor reversed CCDC26 knockdown-induced inhibition of thyroid cancer progression in vitro. CCDC26 upregulated EZH2 and Sirt6 expression by sponging miR-422a in thyroid cancer cells. Tumorigenicity analysis in nude mice revealed that CCDC26 contributed to thyroid tumor growth via miR-422a/EZH2/ Sirt6 axis in vivo. Conclusion: CCDC26 promotes thyroid cancer malignant progression via miR-422a/EZH2/ Sirt6 axis. This finding provides new insights into the mechanism by which CCDC26 promotes malignant thyroid cancer development, advances our understanding of lncRNAs' association with thyroid cancer, and indicates that CCDC26 and miR-422a may serve as potential targets for thyroid cancer.