miR-592 acts as an oncogene and promotes medullary thyroid cancer tumorigenesis by targeting cyclin-dependent kinase 8
miR-592 acts as an oncogene and promotes medullary thyroid cancer tumorigenesis by targeting cyclin-dependent kinase 8
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DOI：
10.3892/mmr.2020.11392
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发表时间：
2020-10-01
影响因子：
3.4
通讯作者：
Zhang, Yu
中科院分区：
文献类型：
--
作者：
Liu, Ting;Meng, Jingjing;Zhang, Yu
甲状腺髓样癌（MTC）是一种相对罕见的甲状腺癌亚型，占全球甲状腺癌所有病例的5-10%。由于目前对MTC的肿瘤发生机制缺乏了解，MTC的临床治疗仍然是一个挑战。据报道，microRNAs （miRNAs）调节MTC的进展；然而，mirna的调控网络和确切的潜在机制尚不完全清楚。在本研究中，我们下载了包含80个样本的miRNA表达谱（GSE40807），并使用Gene expression Omnibus-2R对其进行分析，以鉴定MTC和正常样本之间表达差异的miRNA。与正常组织和细胞系相比，miR-592在MTC组织和细胞系中的表达水平显著升高。与miR-592低表达的患者相比，miR-592高表达的患者预后较差。结果表明，miR-592过表达促进体外TT和MZ-CRC-1细胞增殖。此外，miR-592通过靶向结合在MTC细胞中负调控细胞周期蛋白依赖性激酶8 （CDK8）。此外，共转染CDK8过表达质粒和miR-592模拟逆转miR-592介导的MTC细胞增殖。总之，miR-592可能通过降低CDK8的表达而在MTC中起癌基因的作用，这表明miR-592/CDK8轴可能是MTC的一个有希望的治疗靶点。
Medullary thyroid carcinoma (MTC) is a relatively rare subtype of thyroid cancer, accounting for 5-10% of all cases of thyroid cancer worldwide. Due to the current lack of knowledge regarding the tumorigenesis of MTC, the clinical treatment of MTC remains a challenge. It has been reported that microRNAs (miRNAs) regulate the progression of MTC; however, the regulatory network of miRNAs and the exact underlying mechanisms are not completely understood. In the present study, an miRNA expression profile (GSE40807), consisting of 80 samples, was downloaded and analyzed using Gene Expression Omnibus-2R to identify differentially expressed miRNAs between MTC and normal samples. miR-592 expression levels were significantly increased in MTC tissues and cell lines compared with normal tissues and cell lines. Patients with high miR-592 expression levels exhibited a less favorable prognosis compared with patients with low miR-592 expression. The results suggested that miR-592 overexpression promoted TT and MZ-CRC-1 cell proliferation in vitro. In addition, miR-592 negatively regulated cyclin-dependent kinase 8 (CDK8) via targeted binding in MTC cells. Moreover, co-transfection of CDK8 overexpression plasmid and miR-592 mimic reversed miR-592-mediated MTC cell proliferation. In conclusion, miR-592 may serve as an oncogene in MTC by decreasing the expression of CDK8, indicating that the miR-592/CDK8 axis might serve as a promising therapeutic target for MTC.