Home > Archive>Volume 13, Issue 3, 2020 >374-381. DOI:10.18240/ijo.2020.03.02
PDF HTML XML Export Cite reminder
Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population
Author:
Corresponding Author:

Xing-Chao Shentu. Eye Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. stxc@zju.edu.cn

Fund Project:

Supported by the National Natural Science Foundation of China (No.81670834; No.81970781; No.81800807; No.81800869); the Natural Science Foundation of Zhejiang Province (No.LY17H090004).

  • Article
    • | |
  • Metrics
    • |
  • Reference [40]
    • |
  • Related [20]
    • | | |
  • Comments
    Abstract:

    AIM: To explore the susceptible association between the insulin-like growth factor-1 receptor (IGF1R) single nucleotide polymorphism (SNP) and age-related cataract (ARC), and investigate the underlying mechanisms in human lens epithelium (HLE) cells. METHODS: Totally 1190 unrelated participants, comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The χ2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, different biological experimental methods, such as cell counting kit 8 (CCK-8) assay, flow cytometry, quantitative real time polymerase chain reaction (Q-PCR) and Western blot, were used to detect cell viability, cell cycle progression and apoptosis in HLE cells or IGF1R knockdown HLE cells. RESULTS: The rs1546713 in IGF1R gene was identified (P=0.046, OR: 1.606, 95%CI: 1.245-2.071), which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclin A, cyclin B, cyclin E and P21. The pro-apoptosis function of IGF1R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins, including Bcl-2, Bax and Caspase-3. CONCLUSION: This study first report that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

    Reference
    1 Bourne RR, Stevens GA, White RA, Smith JL, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, Resnikoff S, Taylor HR. Causes of vision loss worldwide, 1990–2010: a systematic analysis. Lancet Glob Heal 2013;1(6):e339-e349.
    2 Resnikoff S, Pascolini D, Mariotti SP, Pokharel GP. Global magnitude of visual impairment caused by uncorrected refractive errors in 2004. Bull World Health Organ 2008;86(1):63-70.
    3 He M, Wang W, Huang WY. Variations and trends in health burden of visual impairment due to cataract: a global analysis. Invest Ophthalmol Vis Sci 2017;58(10):4299-4306.
    4 Khairallah M, Kahloun R, Bourne R, Limburg H, Flaxman SR, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, Price H, White RA, Wong TY, Resnikoff S, Taylor HR; Vision Loss Expert Group of the Global Burden of Disease Study. Number of people blind or visually impaired by cataract worldwide and in world regions, 1990 to 2010. Invest Ophthalmol Vis Sci 2015;56(11):6762-6769.
    5 Klein BE, Klein R, Linton KL. Prevalence of age-related lens opacities in a population. The Beaver Dam Eye Study. Ophthalmology 1992;99(4):546-552.
    6 Hammond CJ, Duncan DD, Snieder H, de Lange M, West SK, Spector TD, Gilbert CE. The heritability of age-related cortical cataract: the twin eye study. Invest Ophthalmol Vis Sci 2001;42(3):601-605.
    7 Hammond CJ, Snieder H, Spector TD, Gilbert CE. Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. N Engl J Med 2000;342(24):1786-1790.
    8 Shiels A, Hejtmancik JF. Genetics of human cataract. Clin Genet 2013;84(2):120-127.
    9 Liu Q, Guan JZ, Sun Y, Le ZY, Zhang P, Yu D, Liu Y. Insulin-like growth factor 1 receptor-mediated cell survival in hypoxia depends on the promotion of autophagy via suppression of the PI3K/Akt/mTOR signaling pathway. Mol Med Rep 2017;15(4):2136-2142.
    10 Lee JH, Kim JY, Kim SY, Choi SI, Kim KC, Cho EW, Kim IG. APBB1 reinforces cancer stem cell and epithelial-to-mesenchymal transition by regulating the IGF1R signaling pathway in non-small-cell lung cancer cells. Biochem Biophys Res Commun 2017;482(1):35-42.
    11 Zhang MS, Liu JR, Li MJ, Zhang SH, Lu YM, Liang YQ, Zhao K, Li YF. Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells. Exp Ther Med 2018;16(2):1477-1482.
    12 Long L, Rubin R, Baserga R, Brodt P. Loss of the metastatic phenotype in murine carcinoma cells expressing an antisense RNA to the insulin-like growth factor receptor. Cancer Res 1995;55(5):1006-1009.
    13 Basu S, Rajakaruna S, De Arcangelis A, Zhang LP, Georges-Labouesse E, Menko AS. Α6 integrin transactivates insulin-like growth factor receptor-1 (IGF-1R) to regulate caspase-3-mediated lens epithelial cell differentiation initiation. J Biol Chem 2014;289(7):3842-3855.
    14 Chylack LT Jr, Leske MC, McCarthy D, Khu P, Kashiwagi T, Sperduto R. Lens opacities classification system II (LOCS II). Arch Ophthalmol 1989;107(7):991-997.
    15 Iams WT, Lovly CM. Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clin Cancer Res 2015;21(19):4270-4277.
    16 Lee J, Hong EM, Jang JA, Park SW, Koh DH, Choi MH, Jang HJ, Kae SH. Simvastatin induces apoptosis and suppresses insulin-like growth factor 1 receptor in bile duct cancer cells. Gut Liver 2016;10(2):310-317.
    17 Wang S, Wang XX, Wu YJ, Han CS. IGF-1R signaling is essential for the proliferation of cultured mouse spermatogonial stem cells by promoting the G2/M progression of the cell cycle. Stem Cells Dev 2015;24(4):471-483.
    18 Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993;75(1):59-72.
    19 Coppola D, Ouban A, Gilbert-Barness E. Expression of the insulin-like growth factor receptor 1 during human embryogenesis. Fetal Pediatr Pathol 2009;28(2):47-54.
    20 Jacobs DB, Ireland M, Pickett T, Maisel H, Grunberger G. Functional characterization of insulin and IGF-I receptors in chicken lens epithelial and fiber cells. Curr Eye Res 1992;11(12):1137-1145.
    21 Bhuyan DK, Reddy PG, Bhuyan KC. Growth factor receptor gene and protein expressions in the human lens. Mech Ageing Dev 2000;113(3):205-218.
    22 Shiels A, Hejtmancik JF. Mutations and mechanisms in congenital and age-related cataracts. Exp Eye Res 2017;156:95-102.
    23 Ma XY, Jiao XD, Ma ZW, Hejtmancik JF. Polymorphism rs7278468 is associated with age-related cataract through decreasing transcriptional activity of the CRYAA promoter. Sci Rep 2016;6:23206.
    24 Kato H, Sekine Y, Furuya Y, Miyazawa Y, Koike H, Suzuki K. Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor. Biochem Biophys Res Commun 2015;461(1):115-121.
    25 Zang QQ, Zhang L, Gao N, Huang C. Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G2/M, and induces apoptosis in human breast carcinoma MCF-7 cells. J Integr Med 2016;14(1):51-59.
    26 Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T, Rubin R, Efstratiadis A, Baserga R. Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. Mol Cell Biol 1994;14(6):3604-3612.
    27 Bendris N, Lemmers B, Blanchard JM. Cell cycle, cytoskeleton dynamics and beyond: the many functions of cyclins and CDK inhibitors. Cell Cycle 2015;14(12):1786-1798.
    28 Coverley D, Laman, Laskey RA. Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 2002;4(7):523-528.
    29 Yam CH, Fung TK, Poon RY. Cyclin A in cell cycle control and cancer. Cell Mol Life Sci 2002;59(8):1317-1326.
    30 Preya UH, Lee KT, Kim NJ, Lee JY, Jang DS, Choi JH. The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancervia the generation of ROS stress. Chem-Biol Interact 2017;272:72-79.
    31 Itoh T, Ono A, Kawaguchi K, Teraoka S, Harada M, Sumi K, Ando M, Tsukamasa Y, Ninomiya M, Koketsu M, Hashizume T. Phytol isolated from watermelon (Citrullus lanatus) sprouts induces cell death in human T-lymphoid cell line Jurkat cells via S-phase cell cycle arrest. Food Chem Toxicol 2018;115:425-435.
    32 Yu JH, Zhang LY, Ren PY, Zhong T, Li ZL, Wang ZY, Li JL, Liu X, Zhao K, Zhang WY, Yu XF. Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D. Cell Cycle 2015;14(3): 425-436.
    33 Li Y, Yu HY, Han FF, Wang MM, Luo Y, Guo XJ. Biochanin A induces S phase arrest and apoptosis in lung cancer cells. Biomed Res Int 2018;2018:3545376.
    34 Orren DK, Petersen LN, Bohr VA. Persistent DNA damage inhibits S-phase and G2 progression, and results in apoptosis. Mol Biol Cell 1997;8(6):1129-1142.
    35 Zhou D, Yin D, Xiao F, Hao J. Expressions of senescence-associated β-galactosidase and senescence marker protein-30 are associated with lens epithelial cell apoptosis. Med Sci Monit 2015;21:3728-3735.
    36 Galichanin K. Exposure to subthreshold dose of UVR-B induces apoptosis in the lens epithelial cells and does not in the lens cortical fibre cells. Acta Ophthalmol 2017;95(8):834-838.
    37 Li WC, Kuszak JR, Dunn K, Wang RR, Ma W, Wang GM, Spector A, Leib M, Cotliar AM, Weiss M. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals. J Cell Biol 1995;130(1):169-181.
    38 Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999;6(2):99-104.
    39 Siddiqui WA, Ahad A, Ahsan H. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol 2015;89(3):289-317.
    40 Peña-Blanco A, García-Sáez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J 2018;285(3):416-431.
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

Yi-Lei Cui, Xiao-Ning Yu, Xin Zhang,/et al.Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population. Int J Ophthalmol, 2020,13(3):374-381

Copy
Share
Article Metrics
  • Abstract:1838
  • PDF: 644
  • HTML: 0
  • Cited by: 0
Publication History
  • Received:September 22,2019
  • Revised:October 23,2019
  • Online: February 04,2020
You are the 4408527 Visitors
Governing Body：Department of Health, Provincial Government of Shaanxi, China
Organizer：Xi'an Medical Association of China
Address：Room 11707-08, Building 2, Unit 1, Wanda Plaza, No.8 Yanta North Road, Xi'an 710054, Shaanxi Province, China
Fax：(8629)82245172 Phone：(+8629)82245172/82210956
Email：ijopress@163.com
International Journal of Ophthalmology ® 2025 All Rights Reserved   The terms of CC BY-NC-ND 4.0 are applicable to all open access content.