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Her-2 expression regulated by downregulation of miR-9 and which affects chemotherapeutic effect in breast cancer

Cancer Gene Therapy volume 24, pages 194–202 (2017)Cite this article

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Abstract

This study aimed to identify microRNAs (miRs), the deregulated expression of which leads to the activation of oncogenic pathways in human breast cancer (BC). miRs are classes of endogenous, small, noncoding RNAs that regulate gene expression aberrantly in human tumor tissues. A total of 39 out of 123 tumoral and matched uninvolved peritumoral breast specimens from 3 independent subsets of patients were analyzed for the expression of 851 human miRs using an Agilent platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by quantitative polymerase chain reaction. Animal assay was further used to test the role of miR-9 and Her-2 in the pathogenesis of BC. All 39 matched samples were analyzed by unsupervised cluster analysis. This analytical approach identified a signature of miRs (miR-9, miR-148a, miR-31, miR-375, miR-21, miR-135b, miR-196a and miR-196b) that were significantly modulated between tumoral and peritumoral tissues in both subsets of patients. Her-2 protein staining increased in tumoral specimens when miR-9 downregulation correlated with the prognostic value. The ectopic expression of miR-9 inhibited the colony-forming ability, migration and tumor engraftment of BC cells. miR-9 targeted the Her-2 messenger RNA and increased responsiveness of BC cells to docetaxel (DOC) or cyclophosphamide treatment. The ectopic expression of Her-2 protein counteracted the miR-9 proapoptotic activity in response to DOC. These findings suggested that the modulation of aberrant expression of miR-9, which in turn induces oncogenic Her-2 protein activity, might hold promise for preventive and therapeutic management of BC.

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Acknowledgements

This study was funded by a grant from the key scientific and technological project for Jilin Province of China (grant number 20150204081SF).

Author contributions

SL carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. LY carried out the immunoassays. SG participated in the design of the study and performed the statistical analysis. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Mammary Surgery Department of China-Japan Union Hospital of Jilin University, Changchun, PRC

    G Sun, L Sun, Y Liu, H Xing & K Wang

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  1. G Sun
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  2. L Sun
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  3. Y Liu
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  4. H Xing
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  5. K Wang
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Correspondence to H Xing or K Wang.

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Sun, G., Sun, L., Liu, Y. et al. Her-2 expression regulated by downregulation of miR-9 and which affects chemotherapeutic effect in breast cancer. Cancer Gene Ther 24, 194–202 (2017). https://doi.org/10.1038/cgt.2014.82

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