MiR-520h is crucial for DAPK2 regulation and breast cancer progression

C. M. Su, M. Y. Wang, C. C. Hong, H. A. Chen, Y. H. Su, C. H. Wu, M. T. Huang, Y. W. Chang, S. S. Jiang, S. Y. Sung, J. Y. Chang, L. T. Chen, P. S. Chen, J. L. Su

研究成果: Article

20 引文 斯高帕斯(Scopus)

摘要

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

原文English
頁(從 - 到)1134-1142
頁數9
期刊Oncogene
35
發行號9
DOIs
出版狀態Published - 2016 三月 3

    指紋

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

引用此

Su, C. M., Wang, M. Y., Hong, C. C., Chen, H. A., Su, Y. H., Wu, C. H., Huang, M. T., Chang, Y. W., Jiang, S. S., Sung, S. Y., Chang, J. Y., Chen, L. T., Chen, P. S., & Su, J. L. (2016). MiR-520h is crucial for DAPK2 regulation and breast cancer progression. Oncogene, 35(9), 1134-1142. https://doi.org/10.1038/onc.2015.168