PMID- 31814699
OWN - NLM
STAT- MEDLINE
DCOM- 20200619
LR  - 20200619
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 25
DP  - 2019
TI  - Long noncoding RNA glutathione peroxidase 3-antisense inhibits lens epithelial 
      cell apoptosis by upregulating glutathione peroxidase 3 expression in age-related 
      cataract.
PG  - 734-744
AB  - PURPOSE: Age-related cataract (ARC) is the leading cause of visual impairment and 
      blindness worldwide. The apoptosis of lens epithelial cells (LECs) induced by 
      oxidative damage is a major contributing factor to ARC. Long noncoding RNAs 
      (lncRNAs) play important roles in various biologic processes. We aimed to explore 
      the role of glutathione peroxidase 3 (GPX3)-antisense (AS) in ARCs. METHODS: We 
      extracted total RNAs from transparent and age-matched cataractous human lenses 
      and detected lncRNA expression profiles using high-throughput RNA sequencing. The 
      expression of GPX3-AS and GPX3 was detected by quantitative real-time PCR 
      (qRT-PCR). Apoptotic proteins were detected by western blot and 
      immunofluorescence. We treated SRA01/04 cells with H(2)O(2) to mimic oxidative 
      stress and induce cell apoptosis, which was analyzed by flow cytometry and 
      TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The cell counting kit-8 
      (CCK-8) assay was used to detect the viability of SRA01/04 cells. The location of 
      GPX3-AS was determined by fluorescence in situ hybridization (FISH) and cell 
      nuclear and cytoplasmic RNA separation. RESULTS: The lncRNA GPX3-AS, which is 
      located in the nuclei of LECs, was downregulated in cataractous human lenses 
      compared with control lenses, and proapoptotic proteins were expressed at high 
      levels in the anterior lens capsules of ARC tissues. An in vitro study suggested 
      that GPX3-AS inhibited H(2)O(2)-induced SRA01/04 cell apoptosis. As GPX3-AS is 
      transcribed from the AS strand of the GPX3 gene locus, we further revealed its 
      regulatory role in GPX3 expression. GPX3-AS was positively correlated with GPX3 
      expression. In addition, GPX3-AS inhibited H(2)O(2)-induced SRA01/04 cell 
      apoptosis by upregulating GPX3 expression. CONCLUSIONS: In summary, our study 
      revealed that GPX3-AS downregulated the apoptosis of LECs via promoting GPX3 
      expression, implying a novel therapeutic target for ARCs.
CI  - Copyright (c) 2019 Molecular Vision.
FAU - Tu, Yuanyuan
AU  - Tu Y
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
AD  - Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, 
      Jiangsu, China.
FAU - Li, Lele
AU  - Li L
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
FAU - Qin, Bai
AU  - Qin B
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
FAU - Wu, Jian
AU  - Wu J
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
FAU - Cheng, Tianyu
AU  - Cheng T
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
FAU - Kang, Lihua
AU  - Kang L
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
FAU - Guan, Huaijin
AU  - Guan H
AD  - Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191114
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (RNA, Long Noncoding)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.- (GPX3 protein, human)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
SB  - IM
MH  - Aging/*genetics
MH  - Anterior Capsule of the Lens/metabolism/pathology
MH  - Apoptosis/drug effects/*genetics
MH  - Cataract/*genetics
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Epithelial Cells/metabolism/*pathology
MH  - Glutathione Peroxidase/*genetics/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/toxicity
MH  - Lens, Crystalline/*pathology
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Up-Regulation/drug effects/*genetics
PMC - PMC6857780
EDAT- 2019/12/10 06:00
MHDA- 2020/06/20 06:00
PMCR- 2019/01/01
CRDT- 2019/12/10 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2019/11/11 00:00 [accepted]
PHST- 2019/12/10 06:00 [entrez]
PHST- 2019/12/10 06:00 [pubmed]
PHST- 2020/06/20 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 67 [pii]
PST - epublish
SO  - Mol Vis. 2019 Nov 14;25:734-744. eCollection 2019.