MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ.
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.
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Mingrong
M
Lü
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China [3] Department of Pathology, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Keshuo
K
Ding
Department of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, People's Republic of China.
Guofeng
G
Zhang
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Mianmian
M
Yin
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.
Guidong
G
Yao
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Hui
H
Tian
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Jie
J
Lian
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Lin
L
Liu
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Meng
M
Liang
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Tao
T
Zhu
1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China [2] Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, People's Republic of China.
Fei
F
Sun
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D018931:Antineoplastic Agents, Hormonal; C490917:ESRRG protein, human; D004967:Estrogens; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; C064321:cyclic AMP-regulated phosphoprotein 19; D013629:Tamoxifen; D011374:Progesterone