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. 2015 Jul 23;34(30):3895-907.
doi: 10.1038/onc.2014.430. Epub 2014 Dec 22.

MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells

J Cui  1 , Y Yang  2 , H Li  3 , Y Leng  4 , K Qian  4 , Q Huang  5 , C Zhang  6 , Z Lu  1 , J Chen  7 , T Sun  7 , R Wu  1 , Y Sun  1 , H Song  1 , X Wei  8 , P Jing  9 , X Yang  10 , C Zhang  1
Affiliations

MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells

J Cui et al. Oncogene. .

Erratum in

Abstract

miRNAs (microRNAs) are frequently and 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 tumor 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.

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