| First Author | Zhang X | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 5 | Pages | e0217181 |
| PubMed ID | 31120927 | Mgi Jnum | J:275757 |
| Mgi Id | MGI:6313518 | Doi | 10.1371/journal.pone.0217181 |
| Citation | Zhang X, et al. (2019) Norcantharidin regulates ERalpha signaling and tamoxifen resistance via targeting miR-873/CDK3 in breast cancer cells. PLoS One 14(5):e0217181 |
| abstractText | MiR-873/CDK3 has been shown to play a critical role in ERalpha signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERalpha but not ERbeta through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERalpha downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERalpha co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERalpha signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer. |
