Revealing the anti-tumor effect of artificial miRNA p-27-5p on human breast carcinoma cell line T-47D
Journal
International Journal of Molecular Science
Journal Volume
13
Journal Issue
5
Pages
6352-6369
Date Issued
2012
Author(s)
Li, Wen-Hsiung
Chang, Jen-Yun
Hsu, Chung-Cheng
Chang, Ya-Ya
Shih, Arthur Chun-Chieh
Tseng, Chien-Wei
Huang, Hsuan-Cheng
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{norm of matrix} 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. ? 2012 by the authors; licensee MDPI, Basel, Switzerland.
Subjects
Breast cancer; Cell cycle; Cyclin-dependent kinase 4; Exon array; MiR P-27-5p; Retinoblastoma protein
SDGs
Other Subjects
cyclin dependent kinase 4; microRNA; microRNA p27 5p; retinoblastoma protein; unclassified drug; 3' untranslated region; CDK4 protein, human; cyclin dependent kinase 4; microRNA; retinoblastoma protein; 3' untranslated region; antineoplastic activity; article; breast carcinoma; cancer cell culture; cancer growth; cell cycle; cell cycle arrest; cell proliferation; controlled study; down regulation; gene expression; gene targeting; human; human cell; protein modification; protein phosphorylation; protein protein interaction; 3' untranslated region; Breast Neoplasms; drug effects; female; G1 phase cell cycle checkpoint; gene expression regulation; genetics; MCF 7 cell line; metabolism; phosphorylation; tumor cell line; 3' Untranslated Regions; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase 4; Down-Regulation; Female; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; MicroRNAs; Phosphorylation; Retinoblastoma Protein
Publisher
MDPI
Type
journal article