Skip to main content
Log in

MYSM-1 suppresses migration and invasion in renal carcinoma through inhibiting epithelial-mesenchymal transition

  • Original Article
  • Published:
Tumor Biology

Abstract

Renal cell carcinoma (RCC) is the most common malignant renal tumor and is prone to metastasis. However, the molecular variation and mechanism underlying renal cell carcinoma metastasis remains largely unknown. In our previous study, it was found that MYSM-1 was significantly downregulated in renal cell carcinoma tissues as compared with normal renal tissues without metastasis, using proteomics approach. Therefore, we hypothesized that MYSM-1 may suppress the metastasis of renal cell carcinoma in light of paucity of data regarding MYSM-1 in the cancers. In the present study, to confirm the expression status of MYSM-1 in renal cell carcinoma, immunohistochemistry with renal carcinoma tissue microarray was performed. It was shown that MYSM-1 was remarkably decreased in renal carcinoma tissues compared with paired normal control tissues; and that low expression of MYSM-1 was significantly associated with poor overall prognosis and metastasis. To investigate the biological roles of MYSM-1 in vitro in renal carcinoma cell lines, both knockdown using siRNA and over-expression were carried out. It was found that MYSM-1 could suppress the proliferation, migration, and invasion of renal carcinoma cells. In addition, we found that MYSM-1 could inhibit the epithelial-mesenchymal transition. Together, our results demonstrate that MYSM-1 could suppress the metastasis of renal carcinoma cells may be through inhibiting the epithelial-mesenchymal transition (EMT) process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. G. Courthod, M. Tucci, M. Di Maio, G.V. Scagliotti, Papillary renal cell carcinoma: a review of the current therapeutic landscape, Crit Rev Oncol Hematol (2015).

  2. Hutchinson L. Imaging: improving detection of bone metastases in renal cell carcinoma. Nat Rev Clin Oncol. 2015;12:503.

    Article  CAS  PubMed  Google Scholar 

  3. Yoneyama M, Tochio N, Umehara T, Koshiba S, Inoue M, Yabuki T, et al. Structural and functional differences of SWIRM domain subtypes. J Mol Biol. 2007;369:222–38.

    Article  CAS  PubMed  Google Scholar 

  4. Le G, Touzot F, Andre-Schmutz I, Lagresle-Peyrou C, France B, Kermasson L, et al. An in vivo genetic reversion highlights the crucial role of Myb-Like, SWIRM, and MPN domains 1 (MYSM1) in human hematopoiesis and lymphocyte differentiation. J Allergy Clin Immunol. 2015;6749(15):00800–3.

    Google Scholar 

  5. Gatzka M, Tasdogan A, Hainzl A, Allies G, Maity P, Wilms C, et al. Interplay of H2A deubiquitinase 2A-DUB/Mysm1 and the p19(ARF)/p53 axis in hematopoiesis, early T-cell development and tissue differentiation. Cell Death Differ. 2015;22:1451–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. DiTommaso T, Jones LK, Cottle DL, Program WMG, Gerdin AK, Vancollie VE, et al. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse. PLoS Genet. 2014;10:e1004705.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liakath-Ali K, Vancollie VE, Heath E, Smedley DP, Estabel J, Sunter D, et al. Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen. Nat Commun. 2014;5:3540.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Holmseth S, Zhou Y, Follin-Arbelet VV, Lehre KP, Bergles DE, Danbolt NC. Specificity controls for immunocytochemistry: the antigen preadsorption test can lead to inaccurate assessment of antibody specificity. J Histochem Cytochem. 2012;60:174–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hewitt SM, Baskin DG, Frevert CW, Stahl WL, Rosa-Molinar E. Controls for immunohistochemistry: The Histochemical Society’s standards of practice for validation of immunohistochemical assays. J Histochem Cytochem. 2014;62:693–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jiang XX, Nguyen Q, Chou Y, Wang T, Nandakumar V, Yates P, et al. Control of B cell development by the histone H2A deubiquitinase MYSM1. Immunity. 2011;35:883–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nijnik A, Clare S, Hale C, Raisen C, McIntyre RE, Yusa K, et al. The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation. Blood. 2012;119:1370–9.

    Article  CAS  PubMed  Google Scholar 

  12. Nandakumar V, Chou Y, Zang L, Huang XF, Chen SY. Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1. Proc Natl Acad Sci U S A. 2013;110:E3927–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Won H, Nandakumar V, Yates P, Sanchez S, Jones L, Huang XF, et al. Epigenetic control of dendritic cell development and fate determination of common myeloid progenitor by Mysm1. Blood. 2014;124:2647–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang T, Nandakumar V, Jiang XX, Jones L, Yang AG, Huang XF, et al. The control of hematopoietic stem cell maintenance, self-renewal, and differentiation by Mysm1-mediated epigenetic regulation. Blood. 2013;122:2812–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Belle JI, Langlais D, Petrov JC, Pardo M, Jones RG, Gros P, et al. p53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency. Blood. 2015;125:2344–8.

    Article  CAS  PubMed  Google Scholar 

  16. Baker M. Reproducibility crisis: blame it on the antibodies. Nature. 2015;521:274–6.

    Article  CAS  PubMed  Google Scholar 

  17. M.A. Helsby, J.R. Fenn, A.D. Chalmers, Reporting research antibody use: how to increase experimental reproducibility, F1000Res 2 (2013) 153.

Download references

Acknowledgments

The work was supported by National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xin Yao.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

(DOCX 13kb)

Supplementary Table 2

(DOCX 13kb)

Supplementary Table 3

(DOCX 14kb)

Supplementary Fig. 4

Evaluation of the specificity of primary antibody againt MYSM-1 that was used in the present study before immunohistochemistry. (DOCX 704kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, L., Shi, L., Guo, H. et al. MYSM-1 suppresses migration and invasion in renal carcinoma through inhibiting epithelial-mesenchymal transition. Tumor Biol. 37, 15583–15591 (2016). https://doi.org/10.1007/s13277-015-4138-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4138-z

Keywords

Navigation