Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1
- Title
- Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1
- Author
- 임형신
- Keywords
- ceRNA; DNA damage response; oxidative stress; hepatocelluar carcinoma; miR-122
- Issue Date
- 2019-03
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Citation
- FASEB JOURNAL, v. 33, No. 7, Page. 7953-7969
- Abstract
- Long noncoding RNA (lncRNA) capable of controlling antioxidative capacity remains to be investigated.
Nuclear factor erythroid-2–related factor 2 (Nrf2) is a central molecule for cellular defense that increases antioxidative capacity. We identified a novel lncRNA named Nrf2-activating lncRNA (Nrf2-lncRNA) transcribed from
an upstream region of the microRNA 122 gene (MIR122). Nrf2-lncRNA existed in the cytoplasm, suggestive of its
function as a competing endogenous RNA [ceRNA, microRNA (miRNA) sponge]. Nrf2-lncRNA served as a ceRNA
for polo-like kinase (Plk) 2 and cyclin-dependent kinase inhibitor 1 (p21cip1) through binding of miRNA 128 and
miRNA 224, inducing Plk2/Nrf2/p21cip1 complexation for Nrf2 activation in the cells under p53-activating conditions
(i.e., DNA damage and serum deprivation).Nrf2-lncRNAexpression was suppressedwith the initiation of apoptosis,
being a rheostat for cell fate determination. Nrf2-lncRNA levels correlated with the recurrence-free postsurgery
survival rate of patients with hepatocellular carcinoma. Collectively, Nrf2-lncRNA promotes Plk2 and p21cip1
translation by competing for specific miRNAs and activating Nrf2 under surviving conditions from oxidative stress,
implying that Nrf2-lncRNA serves as a fine-tuning rheostat for cell fate decision.—Joo, M. S., Shin, S.-B., Kim, E. J.,
Koo, J. H., Yim, H., Kim, S. G. Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an
miRNA sponge for Plk2 and p21cip1.
- URI
- https://www.fasebj.org/doi/full/10.1096/fj.201802744Rhttps://repository.hanyang.ac.kr/handle/20.500.11754/117410
- ISSN
- 0892-6638; 1530-6860
- DOI
- 10.1096/fj.201802744R
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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