Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Comment on “miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition”

British Journal of Cancer volume 125, pages 618–619 (2021)Cite this article

Subjects

We have read with great interest the recently published manuscript by Zhao and co-workers,1 which investigates the clinical impact and functional relevance of the miR-199b/DDR1/ERK signalling axis in prostate cancer (PCa). In this study, miR-199b downregulation was found significantly associated with metastatic disease and shorter overall survival in PCa patients. At the functional level, miR-199b impaired proliferation, migration and invasion in vitro and tumour growth in vivo. Discoidin domain receptor tyrosine kinase 1 (DDR1) was shown as direct target of miR-199b, and also predicted poor outcome in the patient cohort analysed. Moreover, the authors performed rescue experiments and claimed that the miR-199b functions described above are mediated by the negative regulation of DDR1, which also affects ERK activation status thereby controlling epithelial to mesenchymal transition (EMT). From our point of view, this study provides novel interesting findings, but we feel that there are several issues that merit more discussion.

First of all, one cannot be surprised by the fact that luciferase assays performed by Zhao and colleagues showed a positive result, since DDR1 has been previously identified to be a direct target of miR-199b in several previous works in acute myeloid leukaemia, clear cell renal cell carcinoma, colorectal and breast cancers. Regarding the analysis of the clinical impact of miR-199b, the authors failed to show a multivariate analysis to evaluate if miR-199b and/or DRR1 could serve as independent prognostic markers of poor outcome in PCa. Therefore, their prognostic significance in this disease remains to be fully elucidated in forthcoming studies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Zhao, Z., Zhao, S., Luo, L., Xiang, Q., Zhu, Z., Wang, J. et al. miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition. Br. J. Cancer 124, 982–994 (2021).

    Article  CAS  Google Scholar 

  2. Chao, A., Tsai, C. L., Wei, P. C., Hsueh, S., Chao, A. S., Wang, C. J. et al. Decreased expression of microRNA-199b increases protein levels of SET (protein phosphatase 2A inhibitor) in human choriocarcinoma. Cancer Lett. 291, 99–107 (2010).

    Article  CAS  Google Scholar 

  3. Cristóbal, I., Caramés, C., Rincón, R., Manso, R., Madoz-Gúrpide, J., Torrejón, B. et al. Downregulation of microRNA-199b predicts unfavorable prognosis and emerges as a novel therapeutic target which contributes to PP2A inhibition in metastatic colorectal cancer. Oncotarget 8, 40169–40180 (2017).

    Article  Google Scholar 

  4. Hu, X., Garcia, C., Fazli, L., Gleave, M., Vitek, M. P., Jansen, M. et al. Inhibition of Pten deficient castration resistant prostate cancer by targeting of the SET–PP2A signaling axis. Sci. Rep. 5, 15182 (2015).

    Article  Google Scholar 

  5. González-Alonso, P., Cristóbal, I., Manso, R., Madoz-Gúrpide, J., García-Foncillas, J. & Rojo, F. PP2A inhibition as a novel therapeutic target in castration-resistant prostate cancer. Tumour Biol. 36, 5753–5755 (2015).

    Article  Google Scholar 

  6. Cristóbal, I., Torrejón, B., Rubio, J., Santos, A., Pedregal, M., Caramés, C. et al. Deregulation of SET is associated with tumor progression and predicts adverse outcome in patients with early-stage colorectal cancer. J. Clin. Med. 8, 346 (2019).

    Article  Google Scholar 

  7. Mody, H. R., Hung, S. W., Naidu, K., Lee, H., Gilbert, C. A., Hoang, T. T. et al. SET contributes to the epithelial-mesenchymal transition of pancreatic cancer. Oncotarget 8, 67966–67979 (2017).

    Article  Google Scholar 

  8. Liu, C. Y., Huang, T. T., Chen, Y. T., Chen, J. L., Chu, P. Y., Huang, C. T. et al. Targeting SET to restore PP2A activity disrupts an oncogenic CIP2A-feedforward loop and impairs triple negative breast cancer progression. eBioMedicine 40, 263–275 (2019).

    Article  Google Scholar 

  9. Shen, Q., Cicinnati, V. R., Zhang, X., Iacob, S., Weber, F., Sotiropoulos, G. C. et al. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol. Cancer 9, 227 (2010).

    Article  Google Scholar 

  10. Zhong, J., Huang, R., Su, Z., Zhang, M., Xu, M., Gong, J. et al. Downregulation of miR-199a-5p promotes prostate adeno-carcinoma progression through loss of its inhibition of HIF-1alpha. Oncotarget 8, 83523–83538 (2017).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jimenez Díaz-UAM, Madrid, Spain

    Ion Cristóbal, Andrea Santos & Jaime Rubio

  2. Translational Oncology Division, Oncohealth Institute, IIS-Fundación Jimenez Díaz-UAM, Madrid, Spain

    Ion Cristóbal, Andrea Santos & Jesús García-Foncillas

  3. Medical Oncology Department, University Hospital “Fundacion Jimenez Diaz”, Madrid, Spain

    Jaime Rubio & Jesús García-Foncillas

  4. Pathology Department, IIS-Fundación Jiménez Díaz-UAM, Madrid, Spain

    Federico Rojo

Authors
  1. Ion Cristóbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaime Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federico Rojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesús García-Foncillas
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

I.C., A.S. and J.R. conceived the work and drafted the manuscript. F.R. and J.G.F. designed the work and revised the manuscript. All authors approved the final version of the manuscript and agACKreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding authors

Correspondence to Ion Cristóbal or Jesús García-Foncillas.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent to publish

Not applicable.

Data availability

Not applicable.

Competing interests

The authors declare no competing interests.

Funding information

This work was supported by PI18/00382 and PI16/01468 grants from “Instituto de Salud Carlos III FEDER”.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cristóbal, I., Santos, A., Rubio, J. et al. Comment on “miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition”. Br J Cancer 125, 618–619 (2021). https://doi.org/10.1038/s41416-021-01433-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-021-01433-7

This article is cited by

Search

Advanced search

Quick links