title: miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A.
abstract: Breast cancer is a hormone-dependent cancer and usually treated with endocrine therapy using aromatase inhibitors or anti-estrogens such as tamoxifen. A majority of breast cancer, however, will often fail to respond to endocrine therapy. In the present study, we explored miRNAs associated with endocrine therapy resistance in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and their derivative clones as endocrine therapy resistant cell models, including tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF-7 cells. Notably, miR-21 was the most abundantly expressed miRNA in MCF-7 cells and overexpressed in TamR and LTED cells. We found that miR-378a-3p expression was downregulated in TamR and LTED cells as well as in clinical breast cancer tissues. Additionally, lower expression levels of miR-378a-3p were associated with poor prognosis for tamoxifen-treated patients with breast cancer. GOLT1A was selected as one of the miR-378a-3p candidate target genes by in silico analysis. GOLT1A was overexpressed in breast cancer specimens and GOLT1A-specific siRNAs inhibited the growth of TamR cells. Low GOLT1A levels were correlated with better survival in patients with breast cancer. These results suggest that miR-378a-3p-dependent GOLT1A expression contributes to the mechanisms underlying breast cancer endocrine resistance.
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie-Inoue
authors.affiliation: Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Departments of Pathology and Histotechnology, Tohoku University, Graduate School of Medicine, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
authors.affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
authors.affiliation: Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.affiliation: 1] Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan [2] Departments of Anti-Aging Medicine and Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D020413:3' Untranslated Regions; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use / Q000633:toxicity*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013629:Tamoxifen / Q000627:therapeutic use / Q000633:toxicity*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018931:Antineoplastic Agents, Hormonal; C532413:GOLT1A protein, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D013629:Tamoxifen; D012313:RNA