MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation
Journal
Scientific Reports
Journal Volume
4
Pages
5908
Date Issued
2014
Author(s)
Luo, E.-C.
Chang, Y.-C.
Sher, Y.-P.
Huang, W.-Y.
Chuang, L.-L.
Chiu, Y.-C.
Tsai, M.-H.
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 39-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.
SDGs
Other Subjects
cell cycle protein; microRNA; MIRN769 microRNA, human; N-myc downstream-regulated gene 1 protein; oxygen; signal peptide; apoptosis; binding site; breast tumor; cell hypoxia; cell proliferation; down regulation; female; gene expression regulation; genetics; human; MCF 7 cell line; metabolism; molecular dynamics; nucleotide sequence; physiology; RNA interference; Apoptosis; Base Sequence; Binding Sites; Breast Neoplasms; Cell Cycle Proteins; Cell Hypoxia; Cell Proliferation; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; MCF-7 Cells; MicroRNAs; Molecular Dynamics Simulation; Oxygen; RNA Interference
Publisher
Nature Publishing Group
Type
journal article