Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts

Chien, Ke Hung; Chen, S. J.; Liu, J. H.; Chang, Hua Ming; Woung, Lin‐Chung; Liang, Chang; Chen, J. T.; Lin, Tien-An; Chiou, Shih Hwa; Peng, Chi Hsien

doi:10.1038/eye.2013.90

Cited by 34 publications

(23 citation statements)

References 32 publications

(32 reference statements)

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“…MicroRNAs (miRNAs) are a small non-coding RNA molecules found in plants, animals and some viruses that have functions in RNA silencing and post-transcriptional regulation of gene expression [10]. By binding to specific sequences, usually in the 3′ untranslated region (3′UTR) to degrade the transcription of target genes [11], miRNAs have been demonstrated to play an important role in cataract formation [12][13][14][15]. Although some studies have implicated lncRNAs and miRNAs in cataract formation, there is no published study to the best of our knowledge revealing the relationships between them.…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Jin

Hao²,

Shi

et al. 2017

Cell Physiol Biochem

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Background/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. Methods: Human lens epithelium cells (HLECs) were treated with H 2 O 2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR. The expression of caspase-1 was detected using qRT-PCR, western blot and immunostaining. To confirm our findings in cell cultures, we analysed KCNQ1OT1, miR-214, and caspase-1 expression in lens anterior capsules of both cataract patients and normal controls by qRT-PCR and western blot analysis. Results: We found that the expression of KCNQ1OT1 was increased in both human cataract lens anterior capsular samples and SRA01/04 cell lines treated with H 2 O 2 . Knockdown of KCNQ1OT1 expression significantly suppressed H 2 O 2 -induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. The expression of microRNA-214 (miR-214) was also decreased in cataract lens anterior capsular tissues and H 2 O 2 -induced SRA01/04 cell lines. Knockdown of KCNQ1OT1 significantly increased the expression of miR-214. Conclusions: We demonstrated for the first time that caspase-1 is a functional downstream target of miR-214, and knockdown of KCNQ1OT1 reduced the expression of caspase-1. These results provide evidence that the KCNQ1OT1-miR-214-caspase-1 regulatory network is a novel mechanism for promoting cataract formation.

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Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Jin

Hao²,

Shi

et al. 2017

Cell Physiol Biochem

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“…When miR-34a expression in lens epithelial cells obtained during cataract surgery was measured, it was discovered that miR-34a expression not only increased with age at the time of surgery, but it also correlated with the severity of age-related cataract. 122 The recently discovered Klotho gene family consists of three members that encode type I transmembrane glycoproteins with extracellular b-glycosidase-like domains. Expression of these proteins appears to be a factor in the progression of age-related diseases in mammals.…”

Section: Rna and Epigeneticsmentioning

confidence: 99%

Molecular Processes Implicated in Human Age-Related Nuclear Cataract

Truscott

Friedrich

2019

Invest. Ophthalmol. Vis. Sci.

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Human age-related nuclear cataract is commonly characterized by four biochemical features that involve modifications to the structural proteins that constitute the bulk of the lens: coloration, oxidation, insolubility, and covalent cross-linking. Each of these is progressive and increases as the cataract worsens. Significant progress has been made in understanding the origin of the factors that underpin the loss of lens transparency. Of these four hallmarks of cataract, it is protein-protein cross-linking that has been the most intransigent, and it is only recently, with the advent of proteomic methodology, that mechanisms are being elucidated. A diverse range of cross-linking processes involving several amino acids have been uncovered. Although other hypotheses for the etiology of cataract have been advanced, it is likely that spontaneous decomposition of the structural proteins of the lens, which do not turn over, is responsible for the age-related changes to the properties of the lens and, ultimately, for cataract. Cataract may represent the first and best characterized of a number of human agerelated diseases where spontaneous protein modification leads to ongoing deterioration and, ultimately, a loss of tissue function.

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“…Cataract is the most common cause of blindness worldwide and is closely related to age, and oxidative stress and subsequent formation of reactive oxygen species (ROS) are considered to be the main cause of age-related cataract (1). Its pathogenesis involves environmental exposure and genomic mutations that alter epigenetic patterns, and microRNA is one of them.…”

Section: Introductionmentioning

confidence: 99%

Expression of miR‑34a in cataract rats and its related mechanism

2019

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Expression of miR-34a in cataract rats and its related mechanism were investigated. A total of 30 SD rats were selected and divided into three groups: group A: 2-month-old lucent lens, group B: 18-month-old lucent lens, and group C: 18-month-old naturally occurring cataract lens. The lens was taken and measured by LOC III to determine the degree of lens opacity of the three groups of rats. qPCR was used to detect expression of miR-34a and mRNA of SIRT1 and P53. Western blotting was used to detect the protein expression of SIRT1 and P53. Cell apoptosis was detected by flow cytometry. The lens of rats in group C was more turbid than that of groups A and B (P<0.05). The expression levels of miR-34a and P53 mRNA in the rats lens of group C were significantly higher than those in groups A and B, and the expression of SIRT1 mRNA was significantly lower than that of groups A and group B (P<0.05). Expression of miR-34a in group A was significantly higher than that in group B, the mRNA expression of SIRT1 was significantly lower than that in the lucent lens of 18-month-old rats (P<0.05). The expression of SIRT1 protein in group C was significantly lower than that in groups A and group B, while the expression level of P53 protein in group C was significantly higher than that of groups A and B. The expression of SIRT1 protein in group B was significantly higher than that in group A (P<0.05). The apoptosis rate of group C was higher than that of groups A and group B (P<0.05). In conclusion, the upregulation of expression level of miR-34a is related to cataract occurrence in rats, which may be caused by regulation of SIRT1 protein.

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Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts

Cited by 34 publications

References 32 publications

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Molecular Processes Implicated in Human Age-Related Nuclear Cataract

Expression of miR‑34a in cataract rats and its related mechanism

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