• ISSN 1674-8301
  • CN 32-1810/R
Turn off MathJax
Article Contents
Ruxu Sun, Hongjing Zhu, Ying Wang, Jianan Wang, Chao Jiang, Qiuchen Cao, Yeran Zhang, Yichen Zhang, Songtao Yuan, Qinghuai Liu. Circular RNA expression and the competitive endogenous RNA network in pathological, age-related macular degeneration events: A cross-platform normalization study[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.37.20230010
Citation: Ruxu Sun, Hongjing Zhu, Ying Wang, Jianan Wang, Chao Jiang, Qiuchen Cao, Yeran Zhang, Yichen Zhang, Songtao Yuan, Qinghuai Liu. Circular RNA expression and the competitive endogenous RNA network in pathological, age-related macular degeneration events: A cross-platform normalization study[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.37.20230010

Circular RNA expression and the competitive endogenous RNA network in pathological, age-related macular degeneration events: A cross-platform normalization study

doi: 10.7555/JBR.37.20230010
More Information
  • Corresponding author: Songtao Yuan and Qinghuai Liu, Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tel/Fax: +86-25-68303110 and +86-25-68303160, E-mails: yuansongtao@vip.sina.com and liuqh@njmu.edu.cn
  • Received: 2023-01-16
  • Revised: 2023-02-20
  • Accepted: 2023-02-20
  • Published: 2023-04-28
  • Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used ComBat and Training Distribution Matching to integrate data obtained from the gene expression omnibus (GEO) database. Integrated sequencing data were analyzed by Gene Set Enrichment Analysis (GSEA). Peroxisome and tumor necrosis factor-α (TNF-α) signaling via nuclear factor kappa B (NF-κB) were among the top 10 pathways and were selected to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). A competing endogenous RNA network, related to differentially expressed circRNAs, was then constructed. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway is a common downstream event. The results of the current study may provide insights into the pathological processes that cause atrophic AMD.


  • CLC number: R774.5, Document code: A
    The authors reported no conflict of interests.
    These authors contributed equally to this work.
  • loading
  • [1]
    Mitchell P, Liew G, Gopinath B, et al. Age-related macular degeneration[J]. Lancet, 2018, 392(10153): 1147–1159. doi: 10.1016/S0140-6736(18)31550-2
    Datta S, Cano M, Ebrahimi K, et al. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD[J]. Prog Retin Eye Res, 2017, 60: 201–218. doi: 10.1016/j.preteyeres.2017.03.002
    Zhao C, Yasumura D, Li X, et al. mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice[J]. J Clin Invest, 2011, 121(1): 369–383. doi: 10.1172/JCI44303
    Liu B, Wei L, Meyerle C, et al. Complement component C5a promotes expression of IL-22 and IL-17 from human T cells and its implication in age-related macular degeneration[J]. J Transl Med, 2011, 9: 111. doi: 10.1186/1479-5876-9-111
    Cousins SW, Espinosa-Heidmann DG, Csaky KG. Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization?[J]. Arch Ophthalmol, 2004, 122(7): 1013–1018. doi: 10.1001/archopht.122.7.1013
    Yang L, Wilusz JE, Chen L. Biogenesis and regulatory roles of circular RNAs[J]. Annu Rev Cell Dev Biol, 2022, 38: 263–289. doi: 10.1146/annurev-cellbio-120420-125117
    Chen X, Jiang C, Sun R, et al. Circular noncoding RNA NR3C1 acts as a miR-382–5p sponge to protect RPE functions via regulating PTEN/AKT/mTOR signaling pathway[J]. Mol Ther, 2020, 28(3): 929–945. doi: 10.1016/j.ymthe.2020.01.010
    Dhirachaikulpanich D, Li X, Porter LF, et al. Integrated microarray and RNAseq transcriptomic analysis of retinal pigment epithelium/choroid in age-related macular degeneration[J]. Front Cell Dev Biol, 2020, 8: 808. doi: 10.3389/fcell.2020.00808
    Thompson JA, Tan J, Greene CS. Cross-platform normalization of microarray and RNA-seq data for machine learning applications[J]. PeerJ, 2016, 4: e1621. doi: 10.7717/peerj.1621
    Orozco LD, Chen HH, Cox C, et al. Integration of eQTL and a single-cell atlas in the human eye identifies causal genes for age-related macular degeneration[J]. Cell Rep, 2020, 30(4): 1246–1259.e6. doi: 10.1016/j.celrep.2019.12.082
    Newman AM, Gallo NB, Hancox LS, et al. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks[J]. Genome Med, 2012, 4(2): 16. doi: 10.1186/gm315
    Gálvez JM, Castillo-Secilla D, Herrera LJ, et al. Towards improving skin cancer diagnosis by integrating microarray and RNA-Seq datasets[J]. IEEE J Biomed Health Inform, 2020, 24(7): 2119–2130. doi: 10.1109/JBHI.2019.2953978
    Chen X, Sun R, Yang D, et al. LINC00167 regulates RPE differentiation by targeting the miR-203a-3p/SOCS3 axis[J]. Mol Ther Nucleic Acids, 2020, 19: 1015–1026. doi: 10.1016/j.omtn.2019.12.040
    Kanehisa M, Furumichi M, Tanabe M, et al. KEGG: new perspectives on genomes, pathways, diseases and drugs[J]. Nucleic Acids Res, 2017, 45(D1): D353–D361. doi: 10.1093/nar/gkw1092
    Zhang Y, Li J, Cui Q, et al. Circular RNA hsa_circ_0006091 as a novel biomarker for hepatocellular carcinoma[J]. Bioengineered, 2022, 13(2): 1988–2003. doi: 10.1080/21655979.2021.2006952
    Kim KW, Kim K, Kim HJ, et al. Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family[J]. Proc Natl Acad Sci USA, 2021, 118(47): e2110200118. doi: 10.1073/pnas.2110200118
    Müller C, Charniga C, Temple S, et al. Quantified F-actin morphology is predictive of phagocytic capacity of stem cell-derived retinal pigment epithelium[J]. Stem Cell Rep, 2018, 10(3): 1075–1087. doi: 10.1016/j.stemcr.2018.01.017
    Foltz SM, Greene CS, Taroni JN. Cross-platform normalization enables machine learning model training on microarray and RNA-Seq data simultaneously[J]. Commun Biol, 2023, 6(1): 222. doi: 10.1038/s42003-023-04588-6
    Saddala MS, Lennikov A, Mukwaya A, et al. Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration[J]. Hum Genomics, 2019, 13(1): 15. doi: 10.1186/s40246-019-0199-1
    Perez VL, Caspi RR. Immune mechanisms in inflammatory and degenerative eye disease[J]. Trends Immunol, 2015, 36(6): 354–363. doi: 10.1016/j.it.2015.04.003
    Vogt SD, Curcio CA, Wang L, et al. Retinal pigment epithelial expression of complement regulator CD46 is altered early in the course of geographic atrophy[J]. Exp Eye Res, 2011, 93(4): 413–423. doi: 10.1016/j.exer.2011.06.002
    Ebrahimi KB, Fijalkowski N, Cano M, et al. Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age-related macular degeneration[J]. J Pathol, 2013, 229(5): 729–742. doi: 10.1002/path.4128
    Kozumi K, Kodama T, Murai H, et al. Transcriptomics identify thrombospondin-2 as a biomarker for NASH and advanced liver fibrosis[J]. Hepatology, 2021, 74(5): 2452–2466. doi: 10.1002/hep.31995
    Baek JH, Lim D, Park KH, et al. Quantitative proteomic analysis of aqueous humor from patients with drusen and reticular pseudodrusen in age-related macular degeneration[J]. BMC Ophthalmol, 2018, 18(1): 289. doi: 10.1186/s12886-018-0941-9
    Gadaleta RM, Garcia-Irigoyen O, Cariello M, et al. Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor[J]. EBioMedicine, 2020, 54: 102719. doi: 10.1016/j.ebiom.2020.102719
    Choudhary M, Ismail EN, Yao P, et al. LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target[J]. JCI Insight, 2020, 5(1): e131928. doi: 10.1172/jci.insight.131928
    Lu H, Yang Y, Kuang D, et al. Expression profile of circRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis[J]. BMC Med Genomics, 2022, 15(1): 77. doi: 10.1186/s12920-022-01225-9
    Wen J, Liu J, Wan L, et al. Triptolide inhibits cell growth and inflammatory response of fibroblast-like synoviocytes by modulating hsa-circ-0003353/microRNA-31–5p/CDK1 axis in rheumatoid arthritis[J]. Int Immunopharmacol, 2022, 106: 108616. doi: 10.1016/j.intimp.2022.108616
    Iparraguirre L, Muñoz-Culla M, Prada-Luengo I, et al. Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis[J]. Hum Mol Genetics, 2017, 26(18): 3564–3572. doi: 10.1093/hmg/ddx243
    Duan X, Yu X, Li Z. Circular RNA hsa_circ_0001658 regulates apoptosis and autophagy in gastric cancer through microRNA-182/Ras-related protein Rab-10 signaling axis[J]. Bioengineered, 2022, 13(2): 2387–2397. doi: 10.1080/21655979.2021.2024637
    Lei Q, Liang Z, Lei Q, et al. Analysis of circRNAs profile in TNF-α treated DPSC[J]. BMC Oral Health, 2022, 22(1): 269. doi: 10.1186/s12903-022-02267-2
    Kuschel A, Simon P, Tug S. Functional regulation of HIF‐1α under normoxia—is there more than post‐translational regulation?[J]. J Cell Physiol, 2012, 227(2): 514–524. doi: 10.1002/jcp.22798
    Dong S, Liang S, Cheng Z, et al. ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer[J]. J Exp Clin Cancer Res, 2022, 41(1): 15. doi: 10.1186/s13046-021-02229-6
    Chen G, Liu T, Yu B, et al. CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis[J]. Cell Cycle, 2020, 19(13): 1696–1705. doi: 10.1080/15384101.2020.1772545
    Kurihara T, Westenskow PD, Gantner ML, et al. Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration[J]. eLife, 2016, 5: e14319. doi: 10.7554/eLife.14319
  • JBR-2023-0010-supplementary.pdf
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(9)  / Tables(1)

    Article Metrics

    Article views (89) PDF downloads(33) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint