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微小RNA-544通过靶向阴阳-1抑制间变性甲状腺癌的迁移和侵袭。

miR-544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang-1.

作者信息

Wang Feng, Li Zhiqiang, Sun Bo

机构信息

Department of Gastrointestinal, Thyroid and Breast Surgery, Yantai Laiyang Central Hospital, Yantai, Shandong 265200, P.R. China.

Department of General Surgery, Pingyi County People's Hospital, Linyi, Shandong 273300, P.R. China.

出版信息

Oncol Lett. 2019 Mar;17(3):2983-2992. doi: 10.3892/ol.2019.9915. Epub 2019 Jan 9.

Abstract

Anaplastic thyroid cancer (ATC), with a mean survival time of 6 months, was reported in 2012 to account for 1-2% of all thyroid tumor cases in the US. Understanding the molecular mechanisms underlying carcinogenesis and progression in ATC would contribute to determining novel therapeutic targets. The aberrant expression of microRNA-544 (miR-544) has been demonstrated in various cancer types. However, its expression and biological function in human ATC remain largely unknown. Therefore, the present study investigated the expression, function and molecular mechanism of miR-544 in ATC. Results of reverse transcription-quantitative polymerase chain reaction demonstrated that the expression levels of miR-544 in 40 pairs of surgical specimens and human ATC cell lines were significantly decreased, compared with the normal thyroid tissues and cell line. Functional assays indicated that ectopic expression of miR-544 significantly decreased the viability, proliferation and metastasis of SW1736 cells, whereas miR-544 inhibitor significantly enhanced the viability, proliferation and metastasis of 8305C cells. Furthermore, the present study confirmed that the oncogene Yin Yang-1 (YY1) was a direct target of miR-544. It was further demonstrated that YY1 overexpression rescued the inhibitory effect of progression induced by miR-544 in ATC cells. Finally, study indicated that miR-544 suppressed the tumorigenicity of ATC cells. In conclusion, the present study demonstrated that miR-544 may function as a tumor suppressor in ATC and serve as a future therapeutic target for patients with ATC.

摘要

间变性甲状腺癌(ATC)的平均生存时间为6个月,2012年有报道称其在美国所有甲状腺肿瘤病例中占1%-2%。了解ATC致癌和进展的分子机制将有助于确定新的治疗靶点。微小RNA-544(miR-544)在多种癌症类型中均有异常表达。然而,其在人类ATC中的表达及生物学功能仍 largely未知。因此,本研究调查了miR-544在ATC中的表达、功能及分子机制。逆转录-定量聚合酶链反应结果表明,与正常甲状腺组织和细胞系相比,40对手术标本及人类ATC细胞系中miR-544的表达水平显著降低。功能分析表明,miR-544的异位表达显著降低了SW1736细胞的活力、增殖及转移能力,而miR-544抑制剂则显著增强了8305C细胞的活力、增殖及转移能力。此外,本研究证实癌基因阴阳-(YY1)是miR-544的直接靶点。进一步研究表明,YY1过表达可挽救miR-544对ATC细胞进展的抑制作用。最后,研究表明miR-544可抑制ATC细胞的致瘤性。总之,本研究表明miR-544在ATC中可能起抑癌作用,并可作为ATC患者未来的治疗靶点。

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