MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ.

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.

• Authors: Mingrong Lü, Keshuo Ding, Guofeng Zhang, Mianmian Yin, Guidong Yao, Hui Tian, Jie Lian, Lin Liu, Meng Liang, Tao Zhu, Fei Sun
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 8735 (Mar 04 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25736597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• ESRRG protein, human
• Estrogens
• MIRN320 microRNA, human
• MicroRNAs
• Phosphoproteins
• Proto-Oncogene Proteins c-myc
• Receptors, Estrogen
• cyclic AMP-regulated phosphoprotein 19
• Tamoxifen
• Progesterone

Topics

• Animals
• Antineoplastic Agents, Hormonal (pharmacology)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• Drug Resistance, Neoplasm (genetics)
• Estrogens (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Humans
• MCF-7 Cells
• Mice, Nude
• MicroRNAs (genetics)
• Phosphoproteins (genetics, metabolism)
• Progesterone (pharmacology)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Receptors, Estrogen (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tamoxifen (pharmacology)
• Xenograft Model Antitumor Assays (methods)