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Sabotaging of the oxidative stress response by an oncogenic noncoding RNA
- Source :
- The FASEB Journal. 31:482-490
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Overexpression of the multiple myeloma set domain (MMSET) Wolf-Hirschhorn syndrome candidate 1 gene, which contains an orphan box H/ACA class small nucleolar RNA, ACA11, in an intron, is associated with several cancer types, including multiple myeloma (MM). ACA11 and MMSET are overexpressed cotranscriptionally as a result of the t(4;14) chromosomal translocation in a subset of patients with MM. RNA sequencing of CD138+ tumor cells from t(4;14)-positive and -negative MM patient bone marrow samples revealed an enhanced oxidative phosphorylation mRNA signature. Supporting these data, ACA11 overexpression in a t(4;14)-negative MM cell line, MM1.S, demonstrated enhanced reactive oxygen species (ROS) levels. In addition, an enhancement of cell proliferation, increased soft agar colony size, and elevated ERK1/2 phosphorylation were observed. This ACA11-driven hyperproliferative phenotype depended on increased ROS levels as exogenously added antioxidants attenuate the increased proliferation. A major transcriptional regulator of the cellular antioxidant response, nuclear factor (erythroid-derived 2)-like 2 (NRF2), shuttled to the nucleus, as expected, in response to ACA11-driven increases in ROS; however, transcriptional up-regulation of some of NRF2’s antioxidant target genes was abrogated in the presence of ACA11 overexpression. These data show for the first time that ACA11 promotes proliferation through inhibition of NRF2 function resulting in sustained ROS levels driving cancer cell proliferation.—Mahajan, N., Wu, H.-J., Bennett, R. L., Troche, C., Licht, J. D., Weber, J. D., Maggi, L. B., Jr., Tomasson, M. H. Sabotaging of the oxidative stress response by an oncogenic noncoding RNA.
- Subjects :
- 0301 basic medicine
RNA, Untranslated
NF-E2-Related Factor 2
medicine.disease_cause
Biochemistry
Mice
03 medical and health sciences
Cell Line, Tumor
Genetics
Transcriptional regulation
medicine
Animals
Humans
Molecular Biology
Cells, Cultured
Cell Proliferation
Messenger RNA
Cell growth
Chemistry
Research
Intron
RNA
Oncogenes
Fibroblasts
Non-coding RNA
Molecular biology
Oxidative Stress
030104 developmental biology
Gene Expression Regulation
Cancer cell
Multiple Myeloma
Reactive Oxygen Species
Oxidative stress
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....b289929f59553a3fba43db5fc4fb0c96
- Full Text :
- https://doi.org/10.1096/fj.201600654r