title: Revealing the anti-tumor effect of artificial miRNA p-27-5p on human breast carcinoma cell line T-47D.
abstract: microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for cancer. This study investigates the anti-tumor effect of a novel artificial miRNA, miR P-27-5p, on breast cancer. In this study, we reveal that miR P-27-5p downregulates the differential gene expressions associated with the protein modification process and regulation of cell cycle in T-47D cells. Introduction of this novel artificial miRNA, miR P-27-5p, into breast cell lines inhibits cell proliferation and induces the first "gap" phase (G1) cell cycle arrest in cancer cell lines but does not affect normal breast cells. We further show that miR P-27-5p targets the 3'-untranslated mRNA region (3'-UTR) of cyclin-dependent kinase 4 (CDK4) and reduces both the mRNA and protein level of CDK4, which in turn, interferes with phosphorylation of the retinoblastoma protein (RB1). Overall, our data suggest that the effects of miR p-27-5p on cell proliferation and G1 cell cycle arrest are through the downregulation of CDK4 and the suppression of RB1 phosphorylation. This study opens avenues for future therapies targeting breast cancer.
authors: Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors: Chien-Wei
authors: CW
authors: Tseng
authors: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors: Hsuan-Cheng
authors: HC
authors: Huang
authors: Institute of Information Science, Research Center for Information Technology Innovation, Academia Sinica, Taipei 115, Taiwan.
authors: Arthur Chun-Chieh
authors: AC
authors: Shih
authors: Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors: Ya-Ya
authors: YY
authors: Chang
authors: Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors: Chung-Cheng
authors: CC
authors: Hsu
authors: Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors: Jen-Yun
authors: JY
authors: Chang
authors: Biodiversity Research Center and Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA.
authors: Wen-Hsiung
authors: WH
authors: Li
authors: Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors: Hsueh-Fen
authors: 0000-0003-4876-3309
authors: HF
authors: Juan
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000494:pharmacology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016160:Retinoblastoma Protein; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4