We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP<sub>3</sub>.
- Authors
Gan, R; Yang, Y; Yang, X; Zhao, L; Lu, J; Meng, Q H
- 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.
- Subjects
BREAST cancer diagnosis; MICRORNA; REGULATION of body fluids; NEOPLASTIC cell transformation; TAMOXIFEN; TISSUE inhibitors of metalloproteinases; ESTROGEN receptors; CELLULAR pathology
- Publication
Cancer Gene Therapy, 2014, Vol 21, Issue 7, p290
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/cgt.2014.29