Thymosin β10 mediates the effects of microRNA‑184 in the proliferation and epithelial‑mesenchymal transition of BCPAP cells

Yang,Cheng; Liu,Yunni; Fang,Kun

doi:10.3892/etm.2021.10174

Thymosin β10 mediates the effects of microRNA‑184 in the proliferation and epithelial‑mesenchymal transition of BCPAP cells

Authors:
- Cheng Yang
- Yunni Liu
- Kun Fang
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Affiliations: Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China, Department of Surgery, Yinchuan Women and Children's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
Published online on: May 11, 2021 https://doi.org/10.3892/etm.2021.10174
Article Number: 742
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Thyroid cancer is the most common malignant tumor of the endocrine system. It has been reported that thymosin β10 (TMSB10) serves a vital role in tumor invasion and metastasis, and further understanding the role of TMSB10 in thyroid cancer may provide new insights into the development of novel targeted drugs. Bioinformatics analysis suggested that there might exist a regulatory relationship between miR‑184 and TMSB10. Therefore, the expression of microRNA (miR)‑184 was investigated in the TPC‑1 and BCPAP thyroid cancer cell lines and the Nthy‑ori 3‑1 thyroid epithelial cell line via reverse transcription‑quantitative PCR. The effect of miR‑184 on BCPAP cell proliferation was evaluated using MTT and colony formation assays. In addition, the expression levels of epithelial‑mesenchymal transition (EMT)‑associated proteins were examined via western blot analysis and immunofluorescence staining. Furthermore, the targeting association between miR‑184 and TMSB10 was verified using a dual‑luciferase reporter assay. Notably, miR‑184 overexpression attenuated BCPAP cell proliferation, increased the expression level of the epithelial marker E‑cadherin, and decreased that of the mesenchymal marker vimentin. These effects were reversed in BCPAP cells following TMSB10 overexpression. The present study revealed that TMSB10 may be considered as a key mediator in promoting papillary thyroid carcinoma (PTC) cell proliferation and EMT, which were negatively regulated by miR‑184. Therefore, the findings of the present study may provide a novel potential therapeutic target for attenuating PTC cell proliferation.

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1	Davies L and Welch HG: Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 140:317–322. 2014.PubMed/NCBI View Article : Google Scholar
2	Roman BR, Morris LG and Davies L: The thyroid cancer epidemic, 2017 perspective. Curr Opin Endocrinol Diabetes Obes. 24:332–336. 2017.PubMed/NCBI View Article : Google Scholar
3	Cabanillas ME, McFadden DG and Durante C: Thyroid cancer. Lancet. 388:2783–2795. 2016.PubMed/NCBI View Article : Google Scholar
4	Luo L, Xia L, Zha B, Zuo C, Deng D, Chen M, Hu L, He Y, Dai F, Wu J, et al: miR-335-5p targeting ICAM-1 inhibits invasion and metastasis of thyroid cancer cells. Biomed Pharmacother. 106:983–990. 2018.PubMed/NCBI View Article : Google Scholar
5	Li R, Teng X, Zhu H, Han T and Liu Q: MiR-4500 regulates PLXNC1 and inhibits papillary thyroid cancer progression. Horm Cancer. 10:150–160. 2019.PubMed/NCBI View Article : Google Scholar
6	Liu F, Lou K, Zhao X, Zhang J, Chen W, Qian Y, Zhao Y, Zhu Y and Zhang Y: miR-214 regulates papillary thyroid carcinoma cell proliferation and metastasis by targeting PSMD10. Int J Mol Med. 42:3027–3036. 2018.PubMed/NCBI View Article : Google Scholar
7	Minna E, Romeo P, Dugo M, De Cecco L, Todoerti K, Pilotti S, Perrone F, Seregni E, Agnelli L, Neri A, et al: miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma. Oncotarget. 7:12731–12747. 2016.PubMed/NCBI View Article : Google Scholar
8	Qiu Z, Li H, Wang J and Sun C: miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma. Oncol Rep. 38:2735–2740. 2017.PubMed/NCBI View Article : Google Scholar
9	Condello V, Torregrossa L, Sartori C, Denaro M, Poma AM, Piaggi P, Valerio L, Materazzi G, Elisei R, Vitti P and Basolo F: mRNA and miRNA expression profiling of follicular variant of papillary thyroid carcinoma with and without distant metastases. Mol Cell Endocrinol. 479:93–102. 2019.PubMed/NCBI View Article : Google Scholar
10	Zhu HM, Jiang XS, Li HZ, Qian LX, Du MY, Lu ZW, Wu J, Tian XK, Fei Q, He X and Yin L: miR-184 inhibits tumor invasion, migration and metastasis in nasopharyngeal carcinoma by targeting Notch2. Cell Physiol Biochem. 49:1564–1576. 2018.PubMed/NCBI View Article : Google Scholar
11	Wang JX, Gao J, Ding SL, Wang K, Jiao JQ, Wang Y, Sun T, Zhou LY, Long B, Zhang XJ, et al: Oxidative modification of miR-184 enables it to target Bcl-xL and Bcl-w. Mol Cell. 59:50–61. 2015.PubMed/NCBI View Article : Google Scholar
12	Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS and Kalluri R: Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 527:525–530. 2015.PubMed/NCBI View Article : Google Scholar
13	Da C, Wu K, Yue C, Bai P, Wang R, Wang G, Zhao M, Lv Y and Hou P: N-cadherin promotes thyroid tumorigenesis through modulating major signaling pathways. Oncotarget. 8:8131–8142. 2017.PubMed/NCBI View Article : Google Scholar
14	Lv N, Shan Z, Gao Y, Guan H, Fan C, Wang H and Teng W: Twist1 regulates the epithelial-mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma. Endocrine. 51:469–477. 2016.PubMed/NCBI View Article : Google Scholar
15	Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Rodriguez IP, Chakravarthi BVSK and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017.PubMed/NCBI View Article : Google Scholar
16	Zhang XJ, Su YR, Liu D, Xu DB, Zeng MS and Chen WK: Thymosin beta 10 correlates with lymph node metastases of papillary thyroid carcinoma. J Surg Res. 192:487–493. 2014.PubMed/NCBI View Article : Google Scholar
17	Xiao R, Shen S, Yu Y, Pan Q, Kuang R and Huang H: TMSB10 promotes migration and invasion of cancer cells and is a novel prognostic marker for renal cell carcinoma. Int J Clin Exp Pathol. 12:305–312. 2019.PubMed/NCBI
18	Zhang X, Ren D, Guo L, Wang L, Wu S, Lin C, Ye L, Zhu J, Li J, Song L, et al: Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer. Breast Cancer Res. 19(15)2017.PubMed/NCBI View Article : Google Scholar
19	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.PubMed/NCBI View Article : Google Scholar
20	Tang J, Kong D, Cui Q, Wang K, Zhang D, Yuan Q, Liao X, Gong Y and Wu G: Bioinformatic analysis and identification of potential prognostic microRNAs and mRNAs in thyroid cancer. PeerJ. 6(e4674)2018.PubMed/NCBI View Article : Google Scholar
21	Xu Y, Chen J, Yang Z and Xu L: Identification of RNA expression profiles in thyroid cancer to construct a competing endogenous RNA (ceRNA) Network of mRNAs, Long noncoding RNAs (lncRNAs), and microRNAs (miRNAs). Med Sci Monit. 25:1140–1154. 2019.PubMed/NCBI View Article : Google Scholar
22	Lee SM, Na YK, Hong HS, Jang EJ, Yoon GS, Park JY and Kim DS: Hypomethylation of the thymosin β(10) gene is not associated with its overexpression in non-small cell lung cancer. Mol Cells. 32:343–348. 2011.PubMed/NCBI View Article : Google Scholar
23	Song C, Su Z and Guo J: Thymosin β10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma. Biosci Rep. 39(BSR20182355)2019.PubMed/NCBI View Article : Google Scholar
24	Wang B, Wang Z, Zhang T and Yang G: Overexpression of thymosin β10 correlates with disease progression and poor prognosis in bladder cancer. Exp Ther Med. 18:3759–3766. 2019.PubMed/NCBI View Article : Google Scholar
25	Paolillo M and Schinelli S: Extracellular matrix alterations in metastatic processes. Int J Mol Sci. 20(4947)2019.PubMed/NCBI View Article : Google Scholar
26	Pradella D, Naro C, Sette C and Ghigna C: EMT and stemness: Flexible processes tuned by alternative splicing in development and cancer progression. Mol Cancer. 16(8)2017.PubMed/NCBI View Article : Google Scholar
27	Calangiu CM, Simionescu CE, Stepan AE, Cernea D, Zăvoi RE and Mărgăritescu C: The expression of CK19, vimentin and E-cadherin in differentiated thyroid carcinomas. Rom J Morphol Embryol. 55:919–925. 2014.PubMed/NCBI
28	Morillo-Bernal J, Fernandez LP and Santisteban P: FOXE1 regulates migration and invasion in thyroid cancer cells and targets ZEB1. Endocr Relat Cancer. 27:137–151. 2020.PubMed/NCBI View Article : Google Scholar
29	Xia W and Jie W: ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway. Cancer Cell Int. 20(94)2020.PubMed/NCBI View Article : Google Scholar
30	Li T, Zhao N, Lu J, Zhu Q, Liu X, Hao F and Jiao X: Epigallocatechin gallate (EGCG) suppresses epithelial-Mesenchymal transition (EMT) and invasion in anaplastic thyroid carcinoma cells through blocking of TGF-β1/Smad signaling pathways. Bioengineered. 10:282–291. 2019.PubMed/NCBI View Article : Google Scholar
31	Werner TA, Forster CM, Dizdar L, Verde PE, Raba K, Schott M, Knoefel WT and Krieg A: CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma. Br J Cancer. 117:1837–1845. 2017.PubMed/NCBI View Article : Google Scholar
32	Yang Z, Yu W, Huang R, Ye M and Min Z: SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing epithelial-mesenchymal transition. Cancer Cell Int. 19(17)2019.PubMed/NCBI View Article : Google Scholar