Nature Publishing Group
Place of Publication
MiRNAs (microRNAs) are frequently aberrantly expressed in many cancers. MiR-873 has been revealed to be downregulated in colorectal cancer and glioblastoma. However, its function remains unclear. Here, we report that miR-873 is downregulated in breast cancer compared with normal tissue. Enforced expression of miR-873 decreases the transcriptional activity of ER (estrogen receptor) α but not ERβ through the modulation of ERα phosphorylation in ER positive breast cancer cells. We also found that MiR-873 inhibits breast cancer cell proliferation and tumor growth in nude mice. Reporter gene assays revealed cyclin-dependent kinase 3 (CDK3) as a direct target of miR-873. CDK3 was shown to be overexpressed in breast cancer and phosphorylate ERα at Ser104/116 and Ser118. Furthermore, we found that Mir-873 inhibits ER activity and cell growth via targeting CDK3. Interestingly, miR-873 was observed to be downregulated in tamoxifen resistant MCF-7/TamR cells, while CDK3 is overexpressed in these cells. More importantly, re-expression of miR-873 reversed tamoxifen resistance in MCF-7/TamR cells. Our data demonstrate that miR-873 is a novel tumor suppressor in ER positive breast cancer and a potential therapeutic approach for treatment of tamoxifen resistant breast cancer.
Biological Phenomena, Cell Phenomena, and Immunity | Chemistry
J. Cui, M. Bi, A. Overstreet, Y. Yang, H. Li, Y. Leng, K. Qian, Q. Huang, C. Zhang, Z. Lu, J. Chen, R. Wu, Y. Sun, H. Hong, X. Wei, Peng Jing, A. Meredith, X. Yang, and C. Zhang (2014).
MiR-873 Regulates ERα Transcriptional Activity and Tamoxifen Resistance via Targeting CDK3 in Breast Cancer Cells. Oncogene. 1-13. London, UK: Nature Publishing Group.