MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation

En-Ching Luo; Ya-Chu Chang; Yuh-Pyng Sher; Wei-Yung Huang; Li-Ling Chuang; Yu-Chiao Chiu; Mong-Hsun Tsai; Eric Y Chuang; Liang-Chuan Lai

doi:10.1038/srep05908

MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation

Sci Rep. 2014 Aug 1:4:5908. doi: 10.1038/srep05908.

Authors

En-Ching Luo¹, Ya-Chu Chang¹, Yuh-Pyng Sher², Wei-Yung Huang¹, Li-Ling Chuang³, Yu-Chiao Chiu⁴, Mong-Hsun Tsai⁵, Eric Y Chuang⁶, Liang-Chuan Lai⁷

Affiliations

¹ Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
² 1] Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan [2] Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
³ Department of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan.
⁴ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
⁵ 1] Institute of Biotechnology, National Taiwan University, Taipei, Taiwan [2] Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
⁶ 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.
⁷ 1] Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan [2] Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Base Sequence
Binding Sites
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Cell Hypoxia
Cell Proliferation
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / metabolism
MCF-7 Cells
MicroRNAs / physiology*
Molecular Dynamics Simulation
Oxygen / metabolism
RNA Interference*

Substances

Cell Cycle Proteins
Intracellular Signaling Peptides and Proteins
MIRN769 microRNA, human
MicroRNAs
N-myc downstream-regulated gene 1 protein
Oxygen