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

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 impa...

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Veröffentlicht in:Biochemical and biophysical research communications 2018-09, Vol.503 (4), p.2277-2285
Hauptverfasser: Liu, Xin, Liu, Baihui, Zhou, Menglong, Fan, Fan, Yu, Mingrong, Gao, Chao, Lu, Yi, Luo, Yi
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container_issue 4
container_start_page 2277
container_title Biochemical and biophysical research communications
container_volume 503
creator Liu, Xin
Liu, Baihui
Zhou, Menglong
Fan, Fan
Yu, Mingrong
Gao, Chao
Lu, Yi
Luo, Yi
description 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. •CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC.•CircHIPK3 is down-regulated in all three subtypes of ARC.•CircHIPK3 knockdown affects the cellular function in primary cultured HLECs.•CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs.
doi_str_mv 10.1016/j.bbrc.2018.06.149
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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. •CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC.•CircHIPK3 is down-regulated in all three subtypes of ARC.•CircHIPK3 knockdown affects the cellular function in primary cultured HLECs.•CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.06.149</identifier><identifier>PMID: 29959922</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Age-related cataract ; Apoptosis ; Cataract - etiology ; CELL PROLIFERATION ; Cells, Cultured ; circHIPK3 ; Circular RNA ; CRYAA ; Crystallins - metabolism ; Epithelial Cells - cytology ; Human lens epithelial cells ; Humans ; Intracellular Signaling Peptides and Proteins - physiology ; Lens, Crystalline - cytology ; MESSENGER-RNA ; MicroRNAs - metabolism ; miR-193a ; Oxidative Stress ; PATHOGENESIS ; Protein-Serine-Threonine Kinases - physiology ; RNA - physiology</subject><ispartof>Biochemical and biophysical research communications, 2018-09, Vol.503 (4), p.2277-2285</ispartof><rights>2018</rights><rights>Copyright © 2018. 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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. 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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. •CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC.•CircHIPK3 is down-regulated in all three subtypes of ARC.•CircHIPK3 knockdown affects the cellular function in primary cultured HLECs.•CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29959922</pmid><doi>10.1016/j.bbrc.2018.06.149</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3893-1364</orcidid><orcidid>https://orcid.org/0000-0001-6810-5034</orcidid></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
Age-related cataract
Apoptosis
Cataract - etiology
CELL PROLIFERATION
Cells, Cultured
circHIPK3
Circular RNA
CRYAA
Crystallins - metabolism
Epithelial Cells - cytology
Human lens epithelial cells
Humans
Intracellular Signaling Peptides and Proteins - physiology
Lens, Crystalline - cytology
MESSENGER-RNA
MicroRNAs - metabolism
miR-193a
Oxidative Stress
PATHOGENESIS
Protein-Serine-Threonine Kinases - physiology
RNA - physiology
title Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis
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