Biochemical and Biophysical Research Communications
Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis
Introduction
Age related cataract (ARC) is the leading cause of visual impairment and blindness on a global scale [1]. Surgical intervention is the most effective treatment option. However, with the accelerating trend of population aging, the rapid increase of demand for cataract surgery pose great economic burden for society [2]. Thus, it is still required to investigate the potential mechanisms in cataractogenesis for alternative pharmacological means to prevent or delay ARC development.
Circular RNAs (circRNAs) are a novel class of non-coding RNAs characterized by the covalently closed loop structure linking the 3′ and 5′ ends [3]. Circular RNAs participate in a vast range of developmental and physiological processes, including fibrosis, cell apoptosis, proliferation, differentiation, and angiogenesis [4]. Importantly, increasing evidence has shown that aberrant expression of circRNAs are closely associated with the pathogenesis of ocular diseases [[5], [6], [7], [8], [9]]. However, the characterization and function of circRNAs in ARC remain largely unknown.
In this study, we employed circular RNA sequencing technique to identify ARC-related circRNAs. We showed that 101 circRNAs were differentially expressed between transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs. Eight of 10 circRNAs were verified by qRT-PCR. Of them, we characterized one highly conserved circRNA, circHIPK3, and revealed that circHIPK3 knockdown could affect the viability, apoptosis and proliferation of human lens epithelial cells (HLECs), suggesting a potential role of circHIPK3 in ARC formation.
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Ethic statement
The use of human lens samples from postmortem eyes and cataract eyes during surgery was approved by the institutional review board of Eye and ENT Hospital of Fudan University. This study was performed in accordance with the tenets of the Declaration of Helsinki for research involving human subjects. Written informed consents were obtained from every enrolled participant.
Human lens epithelium samples
Lens epithelium samples were obtained from the postmortem eyes (donor age range 50–61 years, free of ocular diseases,
Differential circRNA expression between transparent and ARC lens capsules
Circular RNA sequencing was used to identify ARC-related circRNAs. We set the threshold as the fold change >2.0, and identified 101 differentially expressed circRNAs, including 75 down-regulated circRNAs and 26 up-regulated circRNAs (ARC versus controls; Supplementary Table 2). We then conducted hierarchical clustering analysis to obtain a systematic comparison of circRNA expression between ARC and control group using the top 30 down-regulated and top 20 up-regulated circRNAs (Fig. 1A). Eight
Discussion
Circular RNAs have recently gained attention due to their key roles in the regulation of many biological processes and ocular disorders [4]. However, their roles in ARC are still unclear. In this study, we identified 101 differentially expressed circRNAs between ARC and transparent lens capsules. Of them, circRNA HIPK3 level was down-regulated in ARC capsules. In vitro study revealed the important role of circHIPK3/miR-193a/CRYAA network in regulating HLECs function.
ARC is characterized by
Conflicts of interest
The authors report no conflicts of interest in this work.
Acknowledgments
This study was supported by grants from the National Natural Science Foundation of China (81371002).
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Xin Liu, Baihui Liu and Menglong Zhou contributed equally to this work and should be considered as co-first authors.