MicroRNA-182-5p protects human lens epithelial cells against oxidative stress-induced apoptosis by inhibiting NOX4 and p
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RESEARCH ARTICLE
Open Access
MicroRNA-182-5p protects human lens epithelial cells against oxidative stressinduced apoptosis by inhibiting NOX4 and p38 MAPK signalling Zhao-Na Li1, Ming-Xu Ge2 and Zhong-Fang Yuan3*
Abstract Background: MicroRNAs (miRNAs) are abnormally expressed in various ocular diseases, including age-related cataract. However, the role of miR-182-5p in the progression of age-related cataract remains unclear. Methods: The expression of miR-182-5p in HLE-B3 cells was detected by qRT-PCR. HLE-B3 cells were transfected with miR-182-5p mimics. CCK-8, EdU, flow cytometry, 2′,7′-dichlorodihydrofluorescein diacetate, JC-1 kit, and western blot were used to assess the cell viability, proliferation, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and protein expression, respectively, in vitro. The relationship between miR-182-5p and NOX4 was confirmed using the dual-luciferase reporter gene analysis. Results: We found that miR-182-5p expression was significantly decreased by the H2O2 exposure. Overexpression of miR-182-5p promoted cell proliferation and inhibited ROS production and apoptosis in H2O2-induced HLE-B3 cells. Moreover, p-p-38, p-ERK, and p-JNK were up-regulated in H2O2-treated HLE-B3 cells, and overexpression of miR-1825p reversed the effects of H2O2 on HLE-B3 cells. In addition, dual-luciferase reporter assay substantiated that NOX4 was a direct target and downregulated by miR-182-5p. Conclusions: We concluded that miR-182-5p inhibited lens epithelial cells apoptosis through regulating NOX4 and p38 MAPK signaling, providing a novel biomarker for treatment of age-related cataract. Keywords: Cataract, Oxidative stress, miR-182-5p, NOX4
Background Cataract is characterized by progressive opacity of the ocular lens, which can lead to blindness [1]. Approximately 50% of the blindness in middle-income and lowincome countries is caused by cataracts [2]. Until now, multiple risk factors like aging, diabetes, genetics, oxidative stress and UV exposure have been associated with the pathogenesis of age-related cataract [3]. Although * Correspondence: [email protected] 3 Department of Ophthalmology, Jinan Central Hospital, Affiliate of Shandong University, Jinan, Shandong 250013, People’s Republic of China Full list of author information is available at the end of the article
cataract removal and intraocular lens implantation surgery are effective procedures, letting patients see the light again [4]. However, there are disadvantages in replacing tissues and organs with artificial materials. Surgery may result in severe postoperative complications, including wound leakage, corneal abrasion, and ocular hypertension, especially in the elderly [5]. The number of age-related cataract cases increases from 35.77 million in 1990 to 79.04 million in 2015. It is projected that, by 2050, the number of age-related cataract cases will reach 187.26 million in China [6]. Owing to the prevalence of the disease among ageing populations, cataract surgeries
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