Bi Jian Wei, Zou Yan Liang, Qian Jian Tong, Chen Wen Bin
Department of Pediatrics, Weihaiwei People's Hospital, Weihai, Shandong 264200, P.R. China.
Department of Otolaryngology, Traditional Chinese Medicine Hospital of Juxian, Rizhao, Shandong 276000, P.R. China.
Exp Ther Med. 2019 Oct;18(4):2413-2420. doi: 10.3892/etm.2019.7864. Epub 2019 Aug 7.
Anaplastic thyroid cancer (ATC) has a mean survival time of 6 months and accounts for 1-2% of all thyroid tumors. Understanding the underlying molecular mechanisms of carcinogenesis and progression in ATC would contribute to the identification of novel therapeutic targets. A previous study revealed that microRNA (miR)-599 was associated with tumor initiation and development in certain types of cancer. However, the specific functions and mechanisms of miR-599 in ATC are poorly understood. The objective of the present study was to identify its expression, function and molecular mechanism in ATC. The expression levels of miR-599 in 10 pairs of surgical specimens and human ATC cell lines were examined by reverse transcription-quantitative polymerase chain reaction. Function assays illustrated that miR-599 overexpression not only suppressed KAT-18 cell viability, proliferation and metastasis and decreased tumor growth in the tumor xenograft model but also induced cell apoptosis. Furthermore, T-cell intracellular antigen (TIA1), a tumor suppressor, was confirmed as a direct target of miR-599. It was demonstrated that TIA1 silencing rescued the inhibitory effect of migration and invasion induced by the overexpression of miR-599 in KAT-18 cells. In conclusion, the present study revealed that miR-599 inhibited ATC cell growth and metastasis via activation of TIA1. Therefore miR-599 may be a novel molecular therapeutic target for ATC.
间变性甲状腺癌（ATC）的平均生存时间为6个月，占所有甲状腺肿瘤的1%-2%。了解ATC发生和进展的潜在分子机制将有助于确定新的治疗靶点。先前的一项研究表明，微小RNA（miR）-599与某些类型癌症的肿瘤发生和发展有关。然而，miR-599在ATC中的具体功能和机制尚不清楚。本研究的目的是确定其在ATC中的表达、功能和分子机制。通过逆转录-定量聚合酶链反应检测10对手术标本和人ATC细胞系中miR-599的表达水平。功能分析表明，miR-599过表达不仅抑制了KAT-18细胞的活力、增殖和转移，降低了肿瘤异种移植模型中的肿瘤生长，还诱导了细胞凋亡。此外，肿瘤抑制因子T细胞胞内抗原（TIA1）被证实为miR-599的直接靶点。结果表明，TIA1沉默可挽救miR-599过表达对KAT-18细胞迁移和侵袭的抑制作用。总之，本研究表明miR-599通过激活TIA1抑制ATC细胞的生长和转移。因此，miR-599可能是ATC的一个新的分子治疗靶点。
