title: Bioinformatic and metabolomic analysis reveals miR-155 regulates thiamine level in breast cancer.
abstract: microRNA-155 (miR-155) is one of the well-known oncogenic miRNA implicated in various types of tumors. Thiamine, commonly known as vitamin B1, is one of critical cofactors for energy metabolic enzymes including pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, and transketolase. Here we report a novel role of miR-155 in cancer metabolism through the up-regulation of thiamine in breast cancer cells. A bioinformatic analysis of miRNA array and metabolite-profiling data from NCI-60 cancer cell panel revealed thiamine as a metabolite positively correlated with the miR-155 expression level. We confirmed it in MCF7, MDA-MB-436 and two human primary breast cancer cells by showing reduced thiamine levels upon a knock-down of miR-155. To understand how the miR-155 controls thiamine level, a set of key molecules for thiamine homeostasis were further analyzed after the knockdown of miR-155. The results showed the expression of two thiamine transporter genes (SLC19A2, SLC25A19) as well as thiamine pyrophosphokinase-1 (TPK1) were decreased in both RNA and protein level in miR-155 dependent manner. Finally, we confirm the finding by showing a positive correlation between miR-155 and thiamine level in 71 triple negative breast tumors. Taken altogether, our study demonstrates a role of miR-155 in thiamine homeostasis and suggests a function of this oncogenic miRNA on breast cancer metabolism.
authors.affiliation: Department of Biomedical Sciences, Department of Physiology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sinae
authors.initials: S
authors.lastname: Kim
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Je-keun
authors.initials: JK
authors.lastname: Rhee
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Department of Physiology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Gyungyup
authors.initials: G
authors.lastname: Gong
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Sung Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Stem Cell Regulation and Animal Aging Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
authors.forename: Shree Ram
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Sciences, Department of Physiology, University of Ulsan College of Medicine, Seoul, South Korea; Asan Medical Center, Seoul, South Korea. Electronic address: suhwan.chang@amc.seoul.kr.
authors.forename: Suhwan
authors.initials: S
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D061986:MCF-7 Cells; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D035683:MicroRNAs / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D013836:Thiamin Pyrophosphokinase / Q000235:genetics / Q000378:metabolism; D013831:Thiamine / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C524942:MIRN155 microRNA, human; D026901:Membrane Transport Proteins; D035683:MicroRNAs; D033681:Mitochondrial Membrane Transport Proteins; C120043:SLC19A2 protein, human; C434255:SLC25A19 protein, human; D013836:Thiamin Pyrophosphokinase; D013831:Thiamine
keywords: Breast cancer; SLC19A2; SLC25A19; TPK1; Thiamine; miR-155