Advertisement

Pathology & Oncology Research

, Volume 25, Issue 2, pp 653–658 | Cite as

Triiodothyronine Promotes Cell Proliferation of Breast Cancer via Modulating miR-204/Amphiregulin

  • Li ZhangEmail author
  • Fengxiang Zhang
  • Yanxin Li
  • Xiangjun Qi
  • Yaming Guo
Original Article
  • 58 Downloads

Abstract

Breast cancer (BC) severely threatens women’s life, and Triiodothyronine (T3) shows a positive role on BC cell proliferation, while the potential mechanism underlying it is still unclear. T3 was used to stimulate BC cell lines MCF-7 and T47-D. Real-time PCR was performed to determine the expression of miRNAs, while western blot was used to measure protein expression of Amphiregulin (AREG), AKT and p-AKT. The interaction between miR-204 and AREG was determined using luciferase reporter assay. MTT was performed to detect cell viability. The expression of miR-204 was decreased, while AREG and p-AKT was increased in T3 stimulated BC cell lines. T3 stimulation promoted cell viability. miR-204 targets AREG to regulate its expression. T3 promoted expression of AREG and p-AKT, while miR-204 overexpression reversed the effect of T3, however, pcDNA-AREG transfection abolished the effect of miR-204 mimic. T3 promoted cell viability of BC cells via modulating the AKT signaling pathway. The detailed mechanism was that the down-regulated miR-204 that induced by T3 stimulation promoted the expression of AREG, the up-regulated AREG activated AKT signaling pathway, while the activated AKT signaling promoted cell proliferation.

Keywords

Breast cancer T3 Cell viability miR-204 AREG 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

Not applicable.

References

  1. 1.
    Galton VA, Schneider MJ, Clark AS, St Germain DL (2009) Life without thyroxine to 3,5,3′-triiodothyronine conversion: studies in mice devoid of the 5′-deiodinases. Endocrinology 150:2957–2963CrossRefGoogle Scholar
  2. 2.
    Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeold A, Bianco AC (2008) Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev 29:898–938CrossRefGoogle Scholar
  3. 3.
    Saraiva PP, Figueiredo NB, Padovani CR, Brentani MM, Nogueira CR (2005) Profile of thyroid hormones in breast cancer patients. Braz J Med Biol Res 38:761–765CrossRefGoogle Scholar
  4. 4.
    Dinda S, Sanchez A, Moudgil V (2002) Estrogen-like effects of thyroid hormone on the regulation of tumor suppressor proteins, p53 and retinoblastoma, in breast cancer cells. Oncogene 21:761–768CrossRefGoogle Scholar
  5. 5.
    Conde I, Paniagua R, Zamora J, Blanquez MJ, Fraile B, Ruiz A, Arenas MI (2006) Influence of thyroid hormone receptors on breast cancer cell proliferation. Ann Oncol 17:60–64CrossRefGoogle Scholar
  6. 6.
    Hall LC, Salazar EP, Kane SR, Liu N (2008) Effects of thyroid hormones on human breast cancer cell proliferation. J Steroid Biochem Mol Biol 109:57–66CrossRefGoogle Scholar
  7. 7.
    Rohini M, Gokulnath M, Miranda PJ, Selvamurugan N (2018) MiR-590-3p inhibits proliferation and promotes apoptosis by targeting activating transcription factor 3 in human breast Cancer cells. Biochimie 154:10–18CrossRefGoogle Scholar
  8. 8.
    Yan L, Yu MC, Gao GL, Liang HW, Zhou XY, Zhu ZT, Zhang CY, Wang YB, Chen X (2018) MiR-125a-5p functions as a tumour suppressor in breast cancer by downregulating BAP1. J Cell Biochem 119:8773–8783CrossRefGoogle Scholar
  9. 9.
    Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Pure E, Agami R (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10:202–210CrossRefGoogle Scholar
  10. 10.
    Chen J, Wang BC, Tang JH (2012) Clinical significance of microRNA-155 expression in human breast cancer. J Surg Oncol 106:260–266CrossRefGoogle Scholar
  11. 11.
    Dinami R, Ercolani C, Petti E, Piazza S, Ciani Y, Sestito R, Sacconi A, Biagioni F, le Sage C, Agami R, Benetti R, Mottolese M, Schneider C, Blandino G, Schoeftner S (2014) miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res 74:4145–4156CrossRefGoogle Scholar
  12. 12.
    Mackiewicz M, Huppi K, Pitt JJ, Dorsey TH, Ambs S, Caplen NJ (2011) Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA. Breast Cancer Res Treat 130:663–679CrossRefGoogle Scholar
  13. 13.
    Piovan C, Palmieri D, Di Leva G, Braccioli L, Casalini P, Nuovo G, Tortoreto M, Sasso M, Plantamura I, Triulzi T, Taccioli C, Tagliabue E, Iorio MV, Croce CM (2012) Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer. Mol Oncol 6:458–472CrossRefGoogle Scholar
  14. 14.
    Bai WD, Ye XM, Zhang MY, Zhu HY, Xi WJ, Huang X, Zhao J, Gu B, Zheng GX, Yang AG, Jia LT (2014) MiR-200c suppresses TGF-beta signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer. Int J Cancer 135:1356–1368CrossRefGoogle Scholar
  15. 15.
    Fu J, Xu X, Kang L, Zhou L, Wang S, Lu J, Cheng L, Fan Z, Yuan B, Tian P, Zheng X, Yu C, Ye Q, Lv Z (2014) miR-30a suppresses breast cancer cell proliferation and migration by targeting Eya2. Biochem Biophys Res Commun 445:314–319CrossRefGoogle Scholar
  16. 16.
    Li W, Jin X, Zhang Q, Zhang G, Deng X, Ma L (2014) Decreased expression of miR-204 is associated with poor prognosis in patients with breast cancer. Int J Clin Exp Pathol 7:3287–3292Google Scholar
  17. 17.
    Shen SQ, Huang LS, Xiao XL, Zhu XF, Xiong DD, Cao XM, Wei KL, Chen G, Feng ZB (2017) miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1. Oncol Rep 38:368–376CrossRefGoogle Scholar
  18. 18.
    Willmarth NE, Ethier SP (2008) Amphiregulin as a novel target for breast cancer therapy. J Mammary Gland Biol Neoplasia 13:171–179CrossRefGoogle Scholar
  19. 19.
    Figueiredo NB, Cestari SH, Conde SJ, Luvizotto RA, De Sibio MT, Perone D, Katayama ML, Carraro DM, Brentani HP, Brentani MM, Nogueira CR (2014) Estrogen-responsive genes overlap with triiodothyronine-responsive genes in a breast carcinoma cell line. ScientificWorldJournal 2014:969404Google Scholar
  20. 20.
    Wang X, Masri S, Phung S, Chen S (2008) The role of amphiregulin in exemestane-resistant breast cancer cells: evidence of an autocrine loop. Cancer Res 68:2259–2265CrossRefGoogle Scholar
  21. 21.
    Kondapaka SB, Fridman R, Reddy KB (1997) Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells. Int J Cancer 70:722–726CrossRefGoogle Scholar
  22. 22.
    Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, Grasso G, Blandino R, Panebianco V, Ziparo V, Federici O, Muti P, Strano S, Carboni F, Mottolese M, Diodoro M, Pescarmona E, Garofalo A, Blandino G (2012) miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis 3:e423CrossRefGoogle Scholar
  23. 23.
    Xia Z, Liu F, Zhang J, Liu L (2015) Decreased expression of MiRNA-204-5p contributes to glioma progression and promotes glioma cell growth, migration and invasion. PLoS One 10:e0132399CrossRefGoogle Scholar
  24. 24.
    Wu ZY, Wang SM, Chen ZH, Huv SX, Huang K, Huang BJ, Du JL, Huang CM, Peng L, Jian ZX, Zhao G (2015) MiR-204 regulates HMGA2 expression and inhibits cell proliferation in human thyroid cancer. Cancer Biomark 15:535–542CrossRefGoogle Scholar
  25. 25.
    Guo W, Zhang Y, Zhang Y, Shi Y, Xi J, Fan H, Xu S (2015) Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer. Int J Mol Med 36:1720–1726CrossRefGoogle Scholar
  26. 26.
    Wu L, Chen Z, Xing Y (2018) MiR-506-3p inhibits cell proliferation, induces cell cycle arrest and apoptosis in retinoblastoma by directly targeting NEK6. Cell Biol Int.  https://doi.org/10.1002/cbin.11041
  27. 27.
    Zhou S, Li S, Zhang W, Tong H, Li S, Yan Y (2018) MiR-139 promotes differentiation of bovine skeletal muscle-derived satellite cells by regulating DHFR gene expression. J Cell Physiol 234(1):632–641Google Scholar
  28. 28.
    Frasor J, Stossi F, Danes JM, Komm B, Lyttle CR, Katzenellenbogen BS (2004) Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res 64:1522–1533CrossRefGoogle Scholar
  29. 29.
    Ghazanchaei A, Mansoori B, Mohammadi A, Biglari A, Baradaran B (2018) Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer. J Cell Physiol 234:769–776CrossRefGoogle Scholar
  30. 30.
    Li X, Liu H, Wang J, Qin J, Bai Z, Chi B, Yan W, Chen X (2018) Curcumol induces cell cycle arrest and apoptosis by inhibiting IGF-1R/PI3K/Akt signaling pathway in human nasopharyngeal carcinoma CNE-2 cells. Phytother Res 32(11):2214–2225Google Scholar
  31. 31.
    Kim JW, Kim DK, Min A, Lee KH, Nam HJ, Kim JH, Kim JS, Kim TY, Im SA, Park IA (2016) Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2-positive breast cancer. J Cancer Res Clin Oncol 142(1):157–165Google Scholar

Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Li Zhang
    • 1
    Email author
  • Fengxiang Zhang
    • 1
  • Yanxin Li
    • 1
  • Xiangjun Qi
    • 1
  • Yaming Guo
    • 1
  1. 1.Department of Breast and Thyroid SurgeryTongliao City HospitalTongliaoChina

Personalised recommendations