PUBLICATION
Long non‑coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR‑4728‑5p/OGG1 axis
- Authors
- Zhou, T., Zhang, J., Qin, B., Xu, H., Zhang, S., Guan, H.
- ID
- ZDB-PUB-201002-223
- Date
- 2020
- Source
- International journal of molecular medicine 46: 1838-1848 (Journal)
- Registered Authors
- Xu, Hui, Zhang, Shuqiang, Zhou, Tianqiu
- Keywords
- none
- MeSH Terms
-
- 3' Untranslated Regions/genetics
- Animals
- Cell Line
- DNA Damage/genetics*
- DNA Glycosylases/genetics*
- DNA Glycosylases/metabolism
- DNA Repair/genetics*
- Epithelial Cells/metabolism
- Gene Expression Regulation
- Humans
- Lens, Crystalline/metabolism*
- Lens, Crystalline/pathology
- MicroRNAs/genetics*
- MicroRNAs/metabolism
- Mutation/genetics
- Oxidative Stress/genetics*
- Phenotype
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Ultraviolet Rays
- Zebrafish/genetics
- PubMed
- 33000245 Full text @ Int. J. Mol. Med.
Citation
Zhou, T., Zhang, J., Qin, B., Xu, H., Zhang, S., Guan, H. (2020) Long non‑coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR‑4728‑5p/OGG1 axis. International journal of molecular medicine. 46:1838-1848.
Abstract
Age‑related cataract (ARC) is the leading cause of blindness worldwide. Oxidative DNA damage is a biochemical feature of ARC pathogenesis. The present study investigated the role of long non‑coding RNAs in the DNA repair of oxidative damage, partially the regulation of the DNA repair gene, 8‑oxoguanine DNA glycosylase (OGG1), in lens affected by ARC. The ogg1 mutant zebrafish model was constructed to verify the role of ogg1 in the lens. A high‑throughput lncRNA profiling was performed on human lens epithelial cells (LECs) following oxidative stress. The lncRNAs with the OGG1 target gene were analyzed for possible differentiated expression levels. The lens capsule samples of patients with ARC were collected to further verify the screening results. lncRNA was then overexpressed and knocked down in LECs to observe cell proliferation and apoptosis. The association between lncRNA, miRNA and the OGG1 mRNA 3'UTR were analyzed. The ogg1 mutant zebrafish developed more severe lens lesions following oxidative challenge. lncRNA NONHSAT143692.2 was distinctly expressed in various disease models. The knockdown of NONHSAT143692.2 downregulated the expression of OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001), aggravated oxidative damage to LECs, increased apoptosis (P<0.001) and decreased cell proliferation (P<0.01). The overexpression of NONHSAT143692.2 reversed the above‑mentioned outcomes. miR‑4728‑5p was predicted to bind to NONHSAT143692.2 and OGG1 mRNA 3'UTR. The overexpression of miR‑4728‑5p downregulated the expression of NONHSAT143692.2 (P<0.001), OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001). The knockdown of miR‑4728‑5p reversed the above‑mentioned outcomes. Overall, the findings of the present study demonstrate that the NONHSAT143692.2/miR‑4728‑5p/OGG1 axis may play an important role in the development of ARC. This novel concept may provide new insight into the molecular diagnosis and treatment of ARC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping