title: MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation.
abstract: Hypoxia and reoxygenation are common characteristics of solid tumors, which lead to oxidative stress and activation of stress-response genes. Previously, we observed that N-myc downstream-regulated gene 1 (NDRG1) was strongly down-regulated after shifting to reoxygenation, but the regulatory mechanism of NDRG1 remained elusive. Here we focused on the regulation of NDRG1 by microRNAs (miRNAs). Breast cancer MCF-7 cells were cultured under hypoxia for 24 h followed by 24 h of reoxygenation. The miRNA profiles were examined by Nanostring nCounter assays. Forty-three miRNAs had significant changes upon reoxygenation. In silico analysis identified four oxygen-sensitive miRNAs whose seed regions perfectly matched the 3'-UTR of NDRG1. In particular, miR-769-3p was able to inhibit the expression of NDRG1, which caused a significant reduction of NDRG1 protein upon reoxygenation. Furthermore, overexpression of miR-769-3p significantly inhibited cell proliferation and enhanced apoptosis. Our results revealed that miR-769-3p can functionally regulate NDRG1 during changes in oxygen concentration.
authors: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors: En-Ching
authors: EC
authors: Luo
authors: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors: Ya-Chu
authors: YC
authors: Chang
authors: 1] Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan [2] Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors: Yuh-Pyng
authors: YP
authors: Sher
authors: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors: Wei-Yung
authors: WY
authors: Huang
authors: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan.
authors: Li-Ling
authors: LL
authors: Chuang
authors: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors: Yu-Chiao
authors: YC
authors: Chiu
authors: 1] Institute of Biotechnology, National Taiwan University, Taipei, Taiwan [2] Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors: Mong-Hsun
authors: MH
authors: Tsai
authors: 1] Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan [2] Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors: Eric Y
authors: EY
authors: Chuang
authors: 1] Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan [2] Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors: Liang-Chuan
authors: LC
authors: Lai
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000502:physiology*; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000378:metabolism; D034622:RNA Interference; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D010100:Oxygen; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C546957:MIRN769 microRNA, human