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Biochem Biophys Res Commun. 2018 Sep 18;503(4):2277-2285. doi: 10.1016/j.bbrc.2018.06.149. Epub 2018 Jun 30.

Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis.

Author information

1
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 FenYang Road, Shanghai, 200031, China; Key Laboratory of Myopia, Ministry of Health, 83 FenYang Road, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, 83 FenYang Road, Shanghai, 200031, China.
2
Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
3
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.
4
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 FenYang Road, Shanghai, 200031, China; Key Laboratory of Myopia, Ministry of Health, 83 FenYang Road, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, 83 FenYang Road, Shanghai, 200031, China. Electronic address: yeeluo1106@163.com.

Abstract

Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back splicing. Accumulating evidence has demonstrated their vital regulation in several biological processes and ocular diseases. However, the role of circRNAs in age-related cataract (ARC), the leading cause of visual impairment worldwide, is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially expressed between the capsules of transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10 differentially expressed circRNAs are further verified by quantitative RT-PCRs. One highly conserved circRNA, circHIPK3, is significantly down-regulated in all cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development upon oxidative stress and decreases cell viability and proliferation in primary cultured human lens epithelial cells (HLECs). The expression of α-SMA and vimentin was downregulated, while the expression of E-cadherin and ZO-1was upregulated, suggesting the repression of epithelial-mesenchymal transition after circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a regulates CRYAA expression by targeting the binding site within the 3'UTR. Moreover, miR-193a decreases the viability and proliferation, and increases the apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function through miR-193a-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of ARC.

KEYWORDS:

Age-related cataract; CRYAA; Circular RNA; Human lens epithelial cells; circHIPK3; miR-193a

PMID:
29959922
DOI:
10.1016/j.bbrc.2018.06.149
[Indexed for MEDLINE]

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