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微小RNA-206通过降解间变性甲状腺癌中的MRTF-A抑制转移相关特性。

miR-206 inhibits metastasis-relevant traits by degrading MRTF-A in anaplastic thyroid cancer.

作者信息

Zhang Wen-Long, Lv Wei, Sun Suo-Zhu, Wu Xi-Zhao, Zhang Jian-Hua

机构信息

General Surgery Department, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.

Department of Hepatobiliary Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.

出版信息

Int J Oncol. 2015 Jul;47(1):133-42. doi: 10.3892/ijo.2015.2993. Epub 2015 May 8.

Abstract

Thyroid cancer develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Elucidating molecular mechanism of the disease will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In this study, we found that MRTF-A expression was upregulated in metastatic anaplastic thyroid cancer tissues, compared with primary cancer tissues and it promoted metastasis-relevant traits in vitro. miR-206 was negatively associated with metastasis in anaplastic cancer and it degraded MRTF-A by targeting its 3'-UTR in ARO anaplastic thyroid cancer cells. In addition, miR-206 overexpression inhibited invasion and migration and silencing miR-206-promoted migration and invasion in the cells. Important, restoration of MRTF-A could abrogate miR-206-mediated migration and invasion regulation. Thus, we concluded that miR-206 inhibited invasion and metastasis by degrading MRTF-A in anaplastic thyroid cancer.

摘要

甲状腺癌起源于甲状腺滤泡细胞或滤泡旁细胞。间变性甲状腺癌的比例越高,预后越差。新药正在临床治疗中使用。然而,对于晚期甲状腺恶性肿瘤,如间变性甲状腺癌,成功控制该疾病的主要障碍是缺乏有效的治疗方法。阐明该疾病的分子机制将有助于我们进一步了解疾病的发病机制和进展,并为有效治疗提供新的靶点。在本研究中,我们发现与原发性癌组织相比,MRTF-A在转移性间变性甲状腺癌组织中的表达上调,并且在体外促进了与转移相关的特征。miR-206与间变性癌的转移呈负相关,并且通过靶向ARO间变性甲状腺癌细胞中的MRTF-A的3'-UTR来降解MRTF-A。此外,miR-206过表达抑制细胞的侵袭和迁移,而沉默miR-206则促进细胞的迁移和侵袭。重要的是,恢复MRTF-A可以消除miR-206介导的迁移和侵袭调节。因此,我们得出结论,miR-206通过降解间变性甲状腺癌中的MRTF-A来抑制侵袭和转移。

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