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

Wang,Feng; Li,Zhiqiang; Sun,Bo

doi:10.3892/ol.2019.9915

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

Authors:
- Feng Wang
- Zhiqiang Li
- Bo Sun
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Affiliations: 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
Published online on: January 9, 2019 https://doi.org/10.3892/ol.2019.9915
Pages: 2983-2992

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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, in vivo 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.

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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	O'Neill JP and Shaha AR: Anaplastic thyroid cancer. Oral Oncol. 49:702–706. 2013. View Article : Google Scholar : PubMed/NCBI
3	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
4	Bu Q, You F, Pan G, Yuan Q, Cui T, Hao L and Zhang J: MiR-125b inhibits anaplastic thyroid cancer cell migration and invasion by targeting PIK3CD. Biomed Pharmacother. 88:443–448. 2017. View Article : Google Scholar : PubMed/NCBI
5	Shao M, Geng Y, Lu P, Xi Y, Wei S, Wang L, Fan Q and Ma W: miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A. Biochem Biophys Res Commun. 464:1309–1313. 2015. View Article : Google Scholar : PubMed/NCBI
6	Zhu Z, Wang S, Zhu J, Yang Q, Dong H and Huang J: MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer. Biol Chem. 397:1087–1095. 2016. View Article : Google Scholar : PubMed/NCBI
7	Jin S, Dai Y, Li C, Fang X, Han H and Wang D: MicroRNA-544 inhibits glioma proliferation, invasion and migration but induces cell apoptosis by targeting PARK7. Am J Transl Res. 8:1826–1837. 2016.PubMed/NCBI
8	Mao L, Zhang Y, Deng X, Mo W, Yu Y and Lu H: Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer. Am J Cancer Res. 5:1939–1953. 2015.PubMed/NCBI
9	Ma R, Zhang G, Wang H, Lv H, Fang F and Kang X: Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma. Oncol Lett. 4:1321–1324. 2012. View Article : Google Scholar : PubMed/NCBI
10	Zhi Q, Guo X, Guo L, Zhang R, Jiang J, Ji J, Zhang J, Zhang J, Chen X, Cai Q, et al: Oncogenic miR-544 is an important molecular target in gastric cancer. Anticancer Agents Med Chem. 13:270–275. 2013. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. (4)2015.
13	Brabletz T, Kalluri R, Nieto MA and Weinberg RA: EMT in cancer. Nat Rev Cancer. 18:128–134. 2018. View Article : Google Scholar : PubMed/NCBI
14	Shi Y, Seto E, Chang LS and Shenk T: Transcriptional repression by YY1, a human GLI-Kruppel-related protein and relief of repression by adenovirus E1A protein. Cell. 67:377–388. 1991. View Article : Google Scholar : PubMed/NCBI
15	Gordon S, Akopyan G, Garban H and Bonavida B: Transcription factor YY1: Structure, function, and therapeutic implications in cancer biology. Oncogene. 25:1125–1142. 2006. View Article : Google Scholar : PubMed/NCBI
16	Bonavida B and Kaufhold S: Prognostic significance of YY1 protein expression and mRNA levels by bioinformatics analysis in human cancers: A therapeutic target. Pharmacol Ther. 150:149–168. 2015. View Article : Google Scholar : PubMed/NCBI
17	Seligson D, Horvath S, Huerta-Yepez S, Hanna S, Garban H, Roberts A, Shi T, Liu X, Chia D, Goodglick L and Bonavida B: Expression of transcription factor Yin Yang 1 in prostate cancer. Int J Oncol. 27:131–141. 2005.PubMed/NCBI
18	Kang W, Tong JH, Chan AW, Zhao J, Dong Y, Wang S, Yang W, Sin FM, Ng SS, Yu J, et al: Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma. J Transl Med. 12:802014. View Article : Google Scholar : PubMed/NCBI
19	Allouche A, Nolens G, Tancredi A, Delacroix L, Mardaga J, Fridman V, Winkler R, Boniver J, Delvenne P and Begon DY: The combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors. Breast Cancer Res. 10:R92008. View Article : Google Scholar : PubMed/NCBI
20	Chinnappan D, Xiao D, Ratnasari A, Andry C, King TC and Weber HC: Transcription factor YY1 expression in human gastrointestinal cancer cells. Int J Oncol. 34:1417–1423. 2009.PubMed/NCBI
21	Qu SY, Sun YY, Li YH, Xu ZM and Fu WN: YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress. Cancer Med. 6:1389–1398. 2017. View Article : Google Scholar : PubMed/NCBI
22	Liu D, Zhang J, Wu Y, Shi G, Yuan H, Lu Z, Zhu Q, Wu P, Lu C, Guo F, et al: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway. Int J Cancer. 142:1392–1404. 2018. View Article : Google Scholar : PubMed/NCBI
23	Arribas J, Castellví J, Marcos R, Zafón C and Velázquez A: Expression of YY1 in differentiated thyroid cancer. Endocr Pathol. 26:111–118. 2015. View Article : Google Scholar : PubMed/NCBI