MiR‑599 serves a suppressive role in anaplastic thyroid cancer by activating the T‑cell intracellular antigen

Bi,Jian  Wei; Zou,Yan  Liang; Qian,Jian  Tong; Chen,Wen  Bin

doi:10.3892/etm.2019.7864

MiR‑599 serves a suppressive role in anaplastic thyroid cancer by activating the T‑cell intracellular antigen

Authors:
- Jian Wei Bi
- Yan Liang Zou
- Jian Tong Qian
- Wen Bin Chen
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Affiliations: 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, Department of Otolaryngology, Weihaiwei People's Hospital, Weihai, Shandong 264200, P.R China
Published online on: August 7, 2019 https://doi.org/10.3892/etm.2019.7864
Pages: 2413-2420
Copyright: © Bi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 in vitro 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.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Nagaiah G, Hossain A, Mooney CJ, Parmentier J and Remick SC: Anaplastic thyroid cancer: A review of epidemiology, pathogenesis, and treatment. J Oncol 2011. 5423582011.
3	O'Neill JP and Shaha AR: Anaplastic thyroid cancer. Oral Oncol. 49:702–706. 2013. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
5	Fuziwara CS and Kimura ET: MicroRNAs in thyroid development, function and tumorigenesis. Mol Cell Endocrinol. 456:44–50. 2017. View Article : Google Scholar : PubMed/NCBI
6	Rosignolo F, Memeo L, Monzani F, Colarossi C, Pecce V, Verrienti A, Durante C, Grani G, Lamartina L, Forte S, et al: MicroRNA-based molecular classification of papillary thyroid carcinoma. Int J Oncol. 50:1767–1777. 2017. View Article : Google Scholar : PubMed/NCBI
7	Boufraqech M, Klubo-Gwiezdzinska J and Kebebew E: MicroRNAs in the thyroid. Best Pract Res Clin Endocrinol Metab. 30:603–619. 2016. View Article : Google Scholar : PubMed/NCBI
8	Celano M, Rosignolo F, Maggisano V, Pecce V, Iannone M, Russo D and Bulotta S: MicroRNAs as biomarkers in thyroid carcinoma. Int J Genomics 2017. 64965702017.
9	Wang X, Jin Y, Zhang H, Huang X, Zhang Y and Zhu J: MicroRNA-599 inhibits metastasis and epithelial-mesenchymal transition via targeting EIF5A2 in gastric cancer. Biomed Pharmacother. 97:473–480. 2018. View Article : Google Scholar : PubMed/NCBI
10	Xie B, Zhang C, Kang K and Jiang S: miR-599 inhibits vascular smooth muscle cells proliferation and migration by targeting TGFB2. PLoS One. 10:e01415122015. View Article : Google Scholar : PubMed/NCBI
11	Nelson KM and Weiss GJ: MicroRNAs and cancer: Past, present, and potential future. Mol Cancer Ther. 7:3655–3660. 2008. View Article : Google Scholar : PubMed/NCBI
12	Wang Y, Sui Y, Zhu Q and Sui X: Hsa-miR-599 suppresses the migration and invasion by targeting BRD4 in breast cancer. Oncol Lett. 14:3455–3462. 2017. View Article : Google Scholar : PubMed/NCBI
13	Zhang T, Ma G, Zhang Y, Huo H and Zhao Y: miR-599 inhibits proliferation and invasion of glioma by targeting periostin. Biotechnol Lett. 39:1325–1333. 2017. View Article : Google Scholar : PubMed/NCBI
14	Tian W, Wang G, Liu Y, Huang Z, Zhang C, Ning K, Yu C, Shen Y, Wang M, Li Y, et al: The miR-599 promotes non-small cell lung cancer cell invasion via SATB2. Biochem Biophys Res Commun. 485:35–40. 2017. View Article : Google Scholar : PubMed/NCBI
15	Tian J, Hu X, Gao W, Zhang J, Chen M, Zhang X, Ma J and Yuan H: Identification a novel tumor-suppressive hsa-miR-599 regulates cells proliferation, migration and invasion by targeting oncogenic MYC in hepatocellular carcinoma. Am J Transl Res. 8:2575–2584. 2016.PubMed/NCBI
16	Sánchez-Jiménez C and Izquierdo JM: T-cell intracellular antigens in health and disease. Cell Cycle. 14:2033–2043. 2015. View Article : Google Scholar : PubMed/NCBI
17	Reyes R, Alcalde J and Izquierdo JM: Depletion of T-cell intracellular antigen proteins promotes cell proliferation. Genome Biol. 10:R872009. View Article : Google Scholar : PubMed/NCBI
18	Izquierdo JM, Alcalde J, Carrascoso I, Reyes R and Ludeña MD: Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth. Biochem J. 435:337–344. 2011. View Article : Google Scholar : PubMed/NCBI
19	Hamdollah Zadeh MA, Amin EM, Hoareau-Aveilla C, Domingo E, Symonds KE, Ye X, Heesom KJ, Salmon A, D'Silva O, Betteridge KB, et al: Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance. Mol Oncol. 9:167–178. 2015. View Article : Google Scholar : PubMed/NCBI
20	Liu Y, Liu R, Yang F, Cheng R, Chen X, Cui S, Gu Y, Sun W, You C, Liu Z, et al: miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer. 16:532017. View Article : Google Scholar : PubMed/NCBI
21	Hamada J, Shoda K, Masuda K, Fujita Y, Naruto T, Kohmoto T, Miyakami Y, Watanabe M, Kudo Y, Fujiwara H, et al: Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma. Oncotarget. 7:17111–17128. 2016. View Article : Google Scholar : PubMed/NCBI