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Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3

Cancer Gene Therapy volume 21, pages 290–296 (2014)Cite this article

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A Correction to this article was published on 03 October 2023

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Abstract

Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modulating response to tamoxifen therapy. MCF-7 and MDA-MB-231 breast cancer cells were transfected with antisense oligonucleotides AS-miR-221 and AS-miR-222 and their expression of miR-221 and miR-222 was assessed. The correlation of miR-221/222 with tissue inhibitor of metalloproteinase-3 (TIMP3) expression was investigated by fluorescence quantitative PCR and western blotting analysis. The therapeutic sensitivity of these cells, transfected and untransfected, to tamoxifen was determined. Transfection of AS-miR-221 and AS-miR-222 dramatically inhibited expression of miR-221 and miR-222, respectively, in both MCF-7 and MDA-MB-231 cells (P<0.05–0.01). Downregulation of miR-221/222 significantly increased the expression of TIMP3 compared with controls (P<0.05–0.01). The viability of estrogen receptor (ER)-positive MCF-7 cells transfected with AS-miR-221 or/and AS-miR-222 was significantly reduced by tamoxifen (P<0.05–0.01). We have demonstrated for the first time that suppression of miRNA-221/222 increases the sensitivity of ER-positive MCF-7 breast cancer cells to tamoxifen. This effect is mediated through upregulation of TIMP3. These findings suggest that upregulation of TIMP3 via inhibition of miRNA-221/222 could be a promising therapeutic approach for breast cancer.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81170257) and Zhejiang Provincial Natural Science Foundation (Y2110513).

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Authors and Affiliations

  1. Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, China

    R Gan, Y Yang, X Yang, L Zhao & J Lu

  2. Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, China

    J Lu

  3. Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, China

    J Lu

  4. Department of Laboratory Medicine, The University of Texas MD Anderson Cancer, Houston, TX, USA

    Q H Meng

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  1. R Gan
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Correspondence to J Lu or Q H Meng.

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The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Cancer Gene Therapy website

The original online version of this article was revised: Following the publication of this article, the authors noted that the panel in Figure 1b for AS-miR-221 had mistakenly been placed to show AS-miR-221/222. The correct panel for AS-miR-221/222 has now been included in the below revised figure. The conclusions of the article are unaffected by this correction.

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Gan, R., Yang, Y., Yang, X. et al. Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3. Cancer Gene Ther 21, 290–296 (2014). https://doi.org/10.1038/cgt.2014.29

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