Ma Xiao, Li Yanyan, Song Yuntao, Xu Guohui
Key Laboratory of Carcinogenesis and Translational Research, Department of Head and Neck, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Department of Cardiology, Air Force Medical Center, Beijing, 100036, People's Republic of China.
Onco Targets Ther. 2021 May 11;14:3083-3094. doi: 10.2147/OTT.S282011. eCollection 2021.
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.
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.
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.
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.
长链非编码RNA是甲状腺癌进展的关键调节因子。然而，lncRNA CCDC26在甲状腺癌中的作用仍不清楚。在此，我们旨在探讨CCDC26对甲状腺癌进展的影响及其潜在机制。
使用定量逆转录PCR、CCK-8检测、BrdU掺入检测、Transwell检测、细胞凋亡分析、荧光素酶报告基因检测、RNA免疫沉淀、蛋白质免疫印迹分析和致瘤性分析，对50例临床甲状腺癌样本在患者样本、培养细胞和裸鼠治疗前后进行研究。
CCDC26在患者甲状腺癌组织和甲状腺癌细胞系中表达升高。CCDC26缺失显著降低了甲状腺癌细胞的增殖、侵袭和迁移，但诱导了其凋亡。机制上，miR-422a模拟物显著降低了转染CCDC26细胞的荧光素酶活性，但未能影响转染含有突变miR-422a结合位点的CCDC26的细胞。RNA免疫沉淀（RIP）检测表明，在微小核糖核蛋白复合物（miRNP）中，CCDC26和miR-422a优先与Ago2相互作用，而非IgG。CCDC26缺失增强了miR-422a的表达，MiR-422a抑制剂逆转了CCDC26敲低诱导的体外甲状腺癌进展抑制。CCDC26通过在甲状腺癌细胞中吸附miR-422a上调EZH2和Sirt6的表达。裸鼠致瘤性分析表明，CCDC26在体内通过miR-422a/EZH2/Sirt6轴促进甲状腺肿瘤生长。
CCDC26通过miR-422a/EZH2/Sirt6轴促进甲状腺癌的恶性进展。这一发现为CCDC26促进甲状腺癌恶性发展的机制提供了新的见解，推进了我们对lncRNA与甲状腺癌关联的理解，并表明CCDC26和miR-422a可能作为甲状腺癌的潜在靶点。
