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Hypermethylation of TET1 Promoter Is a New Diagnosic Marker for Breast Cancer Metastasis

  • Sang, Yi (Department of Center Laboratory, the Third Affiliated Hospital, Nanchang University) ;
  • Cheng, Chun (Department of Center Laboratory, the Third Affiliated Hospital, Nanchang University) ;
  • Tang, Xiao-Feng (Department of Center Laboratory, the Third Affiliated Hospital, Nanchang University) ;
  • Zhang, Mei-Fang (State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center) ;
  • Lv, Xiao-Bin (Department of Center Laboratory, the Third Affiliated Hospital, Nanchang University)
  • Published : 2015.03.04

Abstract

Breast cancer metastasis is a major cause of cancer-related death in women. However, markers for diagnosis of breast cancer metastasis are rare. Here, we reported that TET1, a tumor suppressor gene, was downregulated and hypermethylated in highly metastatic breast cancer cell lines. Moreover, silencing of TET1 in breast cancer cells increased the migration and spreading of breast cancer cells. In breast cancer clinical samples, TET1 expression was reduced in LN metastases compared with primary tissues. Besides, the methylation level of the TET1 promoter was increased significantly in LN metastases. Taken together, these findings indicate that promoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promising marker for diagnosis in patients with breast cancer metastasis.

Keywords

TET1;breast cancer metastasis;methylation

References

  1. Cao J, Yang X, Li WT, et al (2014). Silencing of COX-2 by RNAi modulates epithelial-mesenchymal transition in breast cancer cells partially dependent on the PGE2 cascade. Asian Pac J Cancer Prev, 15, 9967-72. https://doi.org/10.7314/APJCP.2014.15.22.9967
  2. Ciccarone F, Valentini E, Bacalini MG, et al (2014). Poly(ADPribosyl) ation is involved in the epigenetic control of TET1 gene transcription. Oncotarget.
  3. Gan H, Wen L, Liao S, et al (2013). Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis. Nat Commun, 4, 1995.
  4. Gong C, Qu S, Lv XB, et al (2014). BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10. Nat Commun, 5, 5406. https://doi.org/10.1038/ncomms6406
  5. He YF, Li BZ, Li Z, et al (2011). Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science, 333, 1303-7. https://doi.org/10.1126/science.1210944
  6. Hong R, Shen MH, Xie XH, et al (2012). Inhibition of breast cancer metastasis via PITPNM3 by pachymic acid. Asian Pac J Cancer Prev, 13, 1877-80. https://doi.org/10.7314/APJCP.2012.13.5.1877
  7. Hsu CH, Peng KL, Kang ML, et al (2012). TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases. Cell Rep, 2, 568-79. https://doi.org/10.1016/j.celrep.2012.08.030
  8. Kudo Y, Tateishi K, Yamamoto K, et al (2012). Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci, 103, 670-6. https://doi.org/10.1111/j.1349-7006.2012.02213.x
  9. Li J, Qiu DM, Chen SH, et al (2014). Suppression of human breast cancer cell metastasis by coptisine in vitro. Asian Pac J Cancer Prev, 15, 5747-51. https://doi.org/10.7314/APJCP.2014.15.14.5747
  10. Lian CG, Xu Y, Ceol C, et al (2012). Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell, 150, 1135-46. https://doi.org/10.1016/j.cell.2012.07.033
  11. Liu Y, Li H, Feng J, et al (2013). Lin28 induces epithelial-tomesenchymal transition and stemness via downregulation of let-7a in breast cancer cells. PLoS One, 8, 83083. https://doi.org/10.1371/journal.pone.0083083
  12. Lv XB, Jiao Y, Qing Y, et al (2011). miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro. Chin J Cancer, 30, 821-30. https://doi.org/10.5732/cjc.011.10289
  13. Mariani CJ, Vasanthakumar A, Madzo J, et al (2014). TET1- mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Rep, 7, 1343-52. https://doi.org/10.1016/j.celrep.2014.04.040
  14. Mercher T, Quivoron C, Couronne L, et al (2012). TET2, a tumor suppressor in hematological disorders. Biochim Biophys Acta, 1825, 173-7.
  15. Pastor WA, Aravind L, Rao A (2013). TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol, 14, 341-56. https://doi.org/10.1038/nrm3589
  16. Sun M, Song CX, Huang H, et al (2013). HMGA2/TET1/ HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proc Natl Acad Sci U S A, 110, 9920-5. https://doi.org/10.1073/pnas.1305172110
  17. Tahiliani M, Koh KP, Shen Y, et al (2009). Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science, 324, 930-5. https://doi.org/10.1126/science.1170116
  18. Truong PK, Lao TD, Doan TP, et al (2014). BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population. Asian Pac J Cancer Prev, 15, 9607-10. https://doi.org/10.7314/APJCP.2014.15.22.9607
  19. Wu H, Zhang Y (2014). Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell, 156, 45-68. https://doi.org/10.1016/j.cell.2013.12.019
  20. Xu Y, Gao XD, Lee JH, et al (2014). Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing. Genes Dev, 28, 1191-203. https://doi.org/10.1101/gad.241968.114
  21. Yang H, Liu Y, Bai F, et al (2013). Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene, 32, 663-9. https://doi.org/10.1038/onc.2012.67

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