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      MiR-30a inhibits BECN1-mediated autophagy in diabetic cataract

      research-article
      Author(s): 1 , 2 , 2 , 3 , 2
      Publication date (Electronic):
      Journal: Oncotarget
      Publisher: Impact Journals LLC
      Keywords: miR-30a, BECN1, autophagy, diabetic cataract, lens epithelial cells

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          Abstract

          Purpose

          To investigate the role of microRNAs in the regulation of autophagy and apoptosis in lens epithelial cells (LECs) during diabetic cataract formation.

          Methods

          A miRNA microarray study and quantitative real-time PCR were performed to identify the expression of miRNAs in LECs of diabetic cataract. Human LECs were cultured in high glucose conditions as a diabetic cataract model. BECN1 and LC3B were detected by Western blotting and quantitative real-time PCR. The extent of apoptosis was measured using FACSCalibur flow cytometry.

          Results

          Downregulation of miR-30a was identified in LECs attached to diabetic cataract tissues. By the bioinformatic assay and the luciferase activity assay, BECN1 was found to be a direct target of miR-30a. MiR-30a reduced the BECN1-mediated autophagy activity induced by high glucose in LECs in vitro. The ratio of LECs apoptosis was also decreased.

          Conclusion

          MiR-30a was involved in the inhibition of autophagy by targeting BECN1 in LECs in human diabetic cataract.

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          Most cited references35

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          Global data on visual impairment in the year 2002.

          Serge Resnikoff, Donatella Pascolini, Daniel Etya'ale … (2004)
          This paper presents estimates of the prevalence of visual impairment and its causes in 2002, based on the best available evidence derived from recent studies. Estimates were determined from data on low vision and blindness as defined in the International statistical classification of diseases, injuries and causes of death, 10th revision. The number of people with visual impairment worldwide in 2002 was in excess of 161 million, of whom about 37 million were blind. The burden of visual impairment is not distributed uniformly throughout the world: the least developed regions carry the largest share. Visual impairment is also unequally distributed across age groups, being largely confined to adults 50 years of age and older. A distribution imbalance is also found with regard to gender throughout the world: females have a significantly higher risk of having visual impairment than males. Notwithstanding the progress in surgical intervention that has been made in many countries over the last few decades, cataract remains the leading cause of visual impairment in all regions of the world, except in the most developed countries. Other major causes of visual impairment are, in order of importance, glaucoma, age-related macular degeneration, diabetic retinopathy and trachoma.
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            A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage.

            H Tanaka, H Arakawa, T. Yamaguchi … (2000)
            The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.
            Article 0 comments Cited 170 times – based on 0 reviews     Review now
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              MicroRNAs and their regulatory roles in animals and plants.

              Baohong Zhang, Qinglian Wang, Xiaoping Pan (2007)
              microRNAs (miRNAs) are an abundant class of newly identified endogenous non-protein-coding small RNAs. They exist in animals, plants, and viruses, and play an important role in gene silencing. Translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-directed deadenylation of targeted mRNAs are three mechanisms of miRNA-guided gene regulation at the post-transcriptional levels. Many miRNAs are highly conserved in animals and plants, suggesting that they play an essential function in plants and animals. Lots of investigations indicate that miRNAs are involved in multiple biological processes, including stem cell differentiation, organ development, phase change, signaling, disease, cancer, and response to biotic and abiotic environmental stresses. This review provides a general background and current advance on the discovery, history, biogenesis, genomics, mechanisms, and functions of miRNAs.
              Article 0 comments Cited 159 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 29 September 2017
                Publication date (Electronic): 24 August 2017
                Volume: 8
                Issue: 44
                Pages: 77360-77368
                Affiliations
                1 Department of Ophthalmology, School of Medicine, Shandong University, Jinan 250012, China
                2 Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China
                3 College of Medicine, Qingdao University, Qingdao 266071, China
                Author notes
                Correspondence to: Yusen Huang, huang_yusen@ 123456126.com
                Article
                Publisher ID: 20483
                DOI: 10.18632/oncotarget.20483
                PMC ID: 5652784
                PubMed ID: 29100392
                SO-VID: 15861170-dbcb-4132-80fd-2f08c8e646b3
                Copyright © Copyright: © 2017 Zhang et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 7 May 2017
                Date accepted : 25 June 2017
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mir-30a,becn1,autophagy,diabetic cataract,lens epithelial cells
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mir-30a, becn1, autophagy, diabetic cataract, lens epithelial cells

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