MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ* View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08

AUTHORS

Mingrong Lü, Keshuo Ding, Guofeng Zhang, Mianmian Yin, Guidong Yao, Hui Tian, Jie Lian, Lin Liu, Meng Liang, Tao Zhu, Fei Sun

ABSTRACT

Tamoxifen represents a major adjuvant therapy to those patients with estrogen receptor-alpha positive breast cancer. However, tamoxifen resistance occurs quite often, either de novo or acquired during treatment. To investigate the role of miR-320a in the development of resistance to tamoxifen, we established tamoxifen-resistant (TamR) models by continually exposing MCF-7 or T47D breast cancer cells to tamoxifen, and identified microRNA(miRNA)-320a as a down-regulated miRNA in tamoxifen resistant cells. Re-expression of miR-320a was sufficient to sensitize TamR cells to tamoxifen by targeting cAMP-regulated phosphoprotein (ARPP-19) and estrogen-related receptor gamma (ERRγ) as well as their downstream effectors, c-Myc and Cyclin D1. Furthermore, progesterone (P4) promoted the expression of miR-320a by repressing c-Myc expression, while estrogen (E2) exerted the opposite effect. These results suggest the potential therapeutic approach for tamoxifen-resistant breast cancer by restorating miR-320a expression or depleting ARPP-19/ERRγ expression. More... »

PAGES

8735

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep08735

DOI

http://dx.doi.org/10.1038/srep08735

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002496447

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25736597


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