The hypoxia-responsive lncRNA NDRG-OT1 promotes NDRG1 degradation via ubiquitin-mediated proteolysis in breast cancer cells
Journal
Oncotarget
Journal Volume
9
Journal Issue
12
Pages
10470-10482
Date Issued
2018
Author(s)
Abstract
Hypoxia can lead to solid tumor aggressiveness by driving multiple signaling pathways. Long non-coding RNAs respond to several extrinsic stimuli, causing changes in cancer cells by participating in multiple steps of gene expression. However, genomic profiling of long non-coding RNAs regulated by oxygen in breast cancer remained unclear. Therefore, the aims of this study were to identify oxygen-responsive long non-coding RNAs in breast cancer cells, and to delineate their regulatory mechanisms. The expression profiling of long non-coding RNAs in breast cancer cells growing under normoxic, hypoxic, and re-oxygenated conditions was examined using next-generation sequencing technology. Four hundred and seventy-two lncRNAs oxygen-responsive lncRNAs were identified. After examining the top three differentially expressed lncRNAs in hypoxia, we selected N-Myc Downstream Regulated Gene 1-Overlapping 1 (NDRG1-OT1) for further study, especially the most responsive isoform, NDRG1-OT1_ v4. We overexpressed NDRG1-OT1_v4 under normoxia and performed microarray analysis to identify 108 NDRG1-OT1_v4 regulated genes and their functions. Among these genes, we found that both NDRG1 mRNA expression and NDRG1 protein levels were inhibited by NDRG1-OT1_v4. Finally, we used co-immunoprecipitation to show that NDRG1-OT1_v4 destabilizes NDRG1 by promoting ubiquitin-mediated proteolysis. Our findings reveal a new type of epigenetic regulation of NDRG1 by NDRG1-OT1_v4 in breast cancer cells. ? Lin et al.
SDGs
Other Subjects
long untranslated RNA; messenger RNA; n myc downstream regulated gene 1 overlapping 1 protein; n myc downstream regulated gene 1 protein; plasmid DNA; ubiquitin; unclassified drug; Article; breast cancer; cancer cell; cancer cell culture; controlled study; gene expression profiling; gene identification; genetic transfection; human; human cell; immunoprecipitation; MCF-7 cell line; microarray analysis; next generation sequencing; protein degradation; regulatory mechanism; reverse transcription polymerase chain reaction; RNA extraction; Western blotting
Publisher
Impact Journals LLC
Type
journal article