Skip to content
2000
image of Bioinformatics Analysis of Lactylation-Related Biomarkers and Potential Pathogenesis Mechanisms in Age-Related Macular Degeneration

Abstract

Background

Lactylation is increasingly recognized to play a crucial role in human health and diseases. However, its involvement in age-related macular degeneration (AMD) remains largely unclear.

Objective

The aim of this study was to identify and characterize the pivotal lactylation-related genes and explore their underlying mechanism in AMD.

Methods

Gene expression profiles of AMD patients and control individuals were obtained and integrated from the GSE29801 and GSE50195 datasets. Differentially expressed genes (DEGs) were screened and intersected with lactylation-related genes for lactylation-related DEGs. Machine learning algorithms were used to identify hub genes associated with AMD. Subsequently, the selected hub genes were subject to correlation analysis, and reverse transcription quantitative real-time PCR (RT-qPCR) was used to detect the expression of hub genes in AMD patients and healthy control individuals.

Results

A total of 68 lactylation-related DEGs in AMD were identified, and seven genes, including ,, , , , , and were selected as key genes. RT-qPCR analysis validated that all 7 key genes were down-regulated in AMD patients.

Conclusion

We identified seven lactylation-related key genes potentially associated with the progression of AMD, which might deepen our understanding of the underlying mechanisms involved in AMD and provide clues for the targeted therapy.

Loading

Article metrics loading...

/content/journals/cg/10.2174/0113892029291661241114055924
2025-01-02
2025-01-22
Loading full text...

Full text loading...

References

  1. Thomas C.J. Mirza R.G. Gill M.K. Age-related macular degeneration. Med. Clin. North Am. 2021 105 3 473 491 10.1016/j.mcna.2021.01.003 33926642
    [Google Scholar]
  2. Stahl A. The diagnosis and treatment of age-related macular degeneration. Dtsch. Arztebl. Int. 2020 117 29-30 513 520 10.3238/arztebl.2020.0513 33087239
    [Google Scholar]
  3. Al-Zamil W. Yassin S. Recent developments in age-related macular degeneration: A review. Clin. Interv. Aging 2017 12 1313 1330 10.2147/CIA.S143508 28860733
    [Google Scholar]
  4. Nashine S. Potential therapeutic candidates for age-related macular degeneration (AMD). Cells 2021 10 9 2483 10.3390/cells10092483 34572131
    [Google Scholar]
  5. Lee Q. Chan W.C. Qu X. Sun Y. Abdelkarim H. Le J. Saqib U. Sun M.Y. Kruse K. Banerjee A. Hitchinson B. Geyer M. Huang F. Guaiquil V. Mutso A.A. Sanders M. Rosenblatt M.I. Maienschein-Cline M. Lawrence M.S. Gaponenko V. Malik A.B. Komarova Y.A. End binding-3 inhibitor activates regenerative program in age-related macular degeneration. Cell Rep. Med. 2023 4 10 101223 10.1016/j.xcrm.2023.101223 37794584
    [Google Scholar]
  6. Williamson R.C. Selvam A. Sant V. Patel M. Bollepalli S.C. Vupparaboina K.K. Sahel J.A. Chhablani J. Radiomics-based prediction of anti-vegf treatment response in neovascular age-related macular degeneration with pigment epithelial detachment. Transl. Vis. Sci. Technol. 2023 12 10 3 10.1167/tvst.12.10.3 37792693
    [Google Scholar]
  7. Rosenfeld P.J. Cheng Y. Shen M. Gregori G. Wang R.K. Unleashing the power of optical attenuation coefficients to facilitate segmentation strategies in OCT imaging of age-related macular degeneration: Perspective. Biomed. Opt. Express 2023 14 9 4947 4963 10.1364/BOE.496080 37791280
    [Google Scholar]
  8. Hamati J. Prashanthi S. Narayanan R. Sahoo N. Das A.V. Rani P.K. Behera U.C. Khanna R. Murthy G.V.S. Prevalence of age-related macular degeneration and associated factors in Indian cohort in a tertiary care setting. Indian J. Ophthalmol. 2023 71 10 3361 3366 10.4103/IJO.IJO_199_23 37787236
    [Google Scholar]
  9. Shaw L. Khanna S. Hyman M.J. Ham S. Blitzer A. Parvar S.P. Soo J. Flores A. Hariprasad S. Skondra D. Interactions of Metformin and other medications in reducing the odds of age-related macular degeneration in a diabetic cohort. Retina 2023 10.1097/IAE.0000000000003949
    [Google Scholar]
  10. Zhao T. Li J. Wang Y. Guo X. Sun Y. Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration. Heliyon 2023 9 10 e20329 10.1016/j.heliyon.2023.e20329 37780745
    [Google Scholar]
  11. Huang Z.W. Zhang X.N. Zhang L. Liu L.L. Zhang J.W. Sun Y.X. Xu J.Q. Liu Q. Long Z.J. STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia. Signal Transduct. Target. Ther. 2023 8 1 391 10.1038/s41392‑023‑01605‑2 37777506
    [Google Scholar]
  12. Zhao S. Liu J. Wu Q. Zhou X. Role of histone lactylation interference RNA m6A modification and immune microenvironment homeostasis in pulmonary arterial hypertension. Front. Cell Dev. Biol. 2023 11 1268646 10.3389/fcell.2023.1268646 37771377
    [Google Scholar]
  13. Su J. Zheng Z. Bian C. Chang S. Bao J. Yu H. Xin Y. Jiang X. Functions and mechanisms of lactylation in carcinogenesis and immunosuppression. Front. Immunol. 2023 14 1253064 10.3389/fimmu.2023.1253064 37646027
    [Google Scholar]
  14. Cheng Z. Huang H. Li M. Liang X. Tan Y. Chen Y. Lactylation-related gene signature effectively predicts prognosis and treatment responsiveness in Hepatocellular Carcinoma. Pharmaceuticals (Basel) 2023 16 5 644 10.3390/ph16050644 37242427
    [Google Scholar]
  15. Wan N. Wang N. Yu S. Zhang H. Tang S. Wang D. Lu W. Li H. Delafield D.G. Kong Y. Wang X. Shao C. Lv L. Wang G. Tan R. Wang N. Hao H. Ye H. Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome. Nat. Methods 2022 19 7 854 864 10.1038/s41592‑022‑01523‑1 35761067
    [Google Scholar]
  16. Liu X. Zhang Y. Li W. Zhou X. Lactylation, an emerging hallmark of metabolic reprogramming: Current progress and open challenges. Front. Cell Dev. Biol. 2022 10 972020 10.3389/fcell.2022.972020 36092712
    [Google Scholar]
  17. Engebretsen S. Bohlin J. Statistical predictions with glmnet. Clin. Epigenetics 2019 11 1 123 10.1186/s13148‑019‑0730‑1 31443682
    [Google Scholar]
  18. Garge N.R. Bobashev G. Eggleston B. Random forest methodology for model-based recursive partitioning: The mobForest package for R. BMC Bioinformatics 2013 14 1 125 10.1186/1471‑2105‑14‑125 23577585
    [Google Scholar]
  19. Sanz H. Valim C. Vegas E. Oller J.M. Reverter F. SVM-RFE: Selection and visualization of the most relevant features through non-linear kernels. BMC Bioinformatics 2018 19 1 432 10.1186/s12859‑018‑2451‑4 30453885
    [Google Scholar]
  20. Urbańska K. Stępień P.W. Nowakowska K.N. Stefaniak M. Osial N. Chorągiewicz T. Toro M.D. Nowomiejska K. Rejdak R. The role of Dysregulated miRNAs in the pathogenesis, diagnosis and treatment of age-related macular degeneration. Int. J. Mol. Sci. 2022 23 14 7761 10.3390/ijms23147761 35887109
    [Google Scholar]
  21. Gemenetzi M. Lotery A.J. Epigenetics in age-related macular degeneration: New discoveries and future perspectives. Cell. Mol. Life Sci. 2020 77 5 807 818 10.1007/s00018‑019‑03421‑w 31897542
    [Google Scholar]
  22. Alfaar A.S. Stürzbecher L. Diedrichs-Möhring M. Lam M. Roubeix C. Ritter J. Schumann K. Annamalai B. Pompös I.M. Rohrer B. Sennlaub F. Reichhart N. Wildner G. Strauß O. FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration. J. Neuroinflammation 2022 19 1 260 10.1186/s12974‑022‑02620‑w 36273134
    [Google Scholar]
  23. Choudhary M. Malek G. Potential therapeutic targets for age-related macular degeneration: The nuclear option. Prog. Retin. Eye Res. 2023 94 101130 10.1016/j.preteyeres.2022.101130 36220751
    [Google Scholar]
  24. Lad E.M. Finger R.P. Guymer R. Biomarkers for the progression of intermediate age-related macular degeneration. Ophthalmol. Ther. 2023 12 6 2917 2941 10.1007/s40123‑023‑00807‑9 37773477
    [Google Scholar]
  25. Nam S.W. Noh H. Yoon J.M. Kong M. Ham D.I. Macular neovascularization in eyes with pachydrusen Sci Rep 2021 11 1 7495
    [Google Scholar]
  26. Interlenghi M. Sborgia G. Venturi A. Sardone R. Pastore V. Boscia G. Landini L. Scotti G. Niro A. Moscara F. Bandi L. Salvatore C. Castiglioni I. A radiomic-based machine learning system to diagnose age-related macular degeneration from ultra-widefield fundus Retinography. Diagnostics (Basel) 2023 13 18 2965 10.3390/diagnostics13182965 37761333
    [Google Scholar]
  27. Ke X. Jiang H. Li Q. Luo S. Qin Y. Li J. Xie Q. Zheng Q. Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. Mol. Ther. 2023 31 11 3308 3321 10.1016/j.ymthe.2023.09.019 37752703
    [Google Scholar]
  28. Vidal-Gil L. Sancho-Pelluz J. Zrenner E. Oltra M. Sahaboglu A. Poly ADP ribosylation and extracellular vesicle activity in rod photoreceptor degeneration. Sci. Rep. 2019 9 1 3758 10.1038/s41598‑019‑40215‑3 30842506
    [Google Scholar]
  29. Karthikeyan B. Harini L. Krishnakumar V. Kannan V.R. Sundar K. Kathiresan T. Insights on the involvement of (–)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration. Apoptosis 2017 22 1 72 85 10.1007/s10495‑016‑1318‑2 27778132
    [Google Scholar]
  30. Kalariya N.M. Ramana K.V. Srivastava S.K. van Kuijk F.J.G.M. Post‐translational protein modification by carotenoid cleavage products. Biofactors 2011 37 2 104 116 10.1002/biof.152 21488133
    [Google Scholar]
  31. Li Y. Zhang R. Hei H. Advances in post-translational modifications of proteins and cancer immunotherapy. Front. Immunol. 2023 14 1229397 10.3389/fimmu.2023.1229397 37675097
    [Google Scholar]
  32. Hou J. Wen X. Long P. Xiong S. Liu H. Cai L. Deng H. Zhang Z. The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude. Front. Cardiovasc. Med. 2022 9 886300 10.3389/fcvm.2022.886300 36186970
    [Google Scholar]
  33. Song Y. Liu X. Stielow J.B. de Hoog S. Li R. Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder. Front. Immunol. 2022 13 966457 10.3389/fimmu.2022.966457 36003392
    [Google Scholar]
  34. Rho H. Terry A.R. Chronis C. Hay N. Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis. Cell Metab. 2023 35 8 1406 1423.e8 10.1016/j.cmet.2023.06.013 37463576
    [Google Scholar]
  35. Zhang N. Zhang Y. Xu J. Wang P. Wu B. Lu S. Lu X. You S. Huang X. Li M. Zou Y. Liu M. Zhao Y. Sun G. Wang W. Geng D. Liu J. Cao L. Sun Y. α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure. Cell Res. 2023 33 9 679 698 10.1038/s41422‑023‑00844‑w 37443257
    [Google Scholar]
  36. Zhang Y. Sun Y. Hu Y. Zheng S. Shao H. Lin L. Pan Y. Li C. Porphyromonas gingivalis msRNA P.G_45033 induces amyloid-β production by enhancing glycolysis and histone lactylation in macrophages. Int. Immunopharmacol. 2023 121 110468 10.1016/j.intimp.2023.110468 37320870
    [Google Scholar]
  37. Huang W. Su J. Chen X. Li Y. Xing Z. Guo L. Li S. Zhang J. High-intensity interval training induces protein Lactylation in different tissues of mice with specificity and time dependence. Metabolites 2023 13 5 647 10.3390/metabo13050647 37233688
    [Google Scholar]
  38. Zhao S. Zhang L. Ji W. Shi Y. Lai G. Chi H. Huang W. Cheng C. Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in parkinson’s disease. Front. Genet. 2022 13 1010361 10.3389/fgene.2022.1010361 36338988
    [Google Scholar]
  39. Yang Y. Yi X. Cai Y. Zhang Y. Xu Z. Immune-associated gene signatures and subtypes to predict the progression of Atherosclerotic Plaques based on machine learning. Front. Pharmacol. 2022 13 865624 10.3389/fphar.2022.865624 35559253
    [Google Scholar]
  40. Bian Q. Chen J. Wu J. Ding F. Li X. Ma Q. Zhang L. Zou X. Chen J. Bioinformatics analysis of a TF-miRNA-lncRNA regulatory network in major depressive disorder. Psychiatry Res. 2021 299 113842 10.1016/j.psychres.2021.113842 33751989
    [Google Scholar]
  41. Zeng Y. Cao S. Li N. Tang J. Lin G. Identification of key lipid metabolism-related genes in alzheimer’s disease. Lipids Health Dis. 2023 22 1 155 10.1186/s12944‑023‑01918‑9 37736681
    [Google Scholar]
  42. Wang X. Chen M. Liu L. Zeng L. Integrated aqueous humor ceRNA and miRNA–TF–mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis. Indian J. Ophthalmol. 2023 71 2 553 559 10.4103/ijo.IJO_1448_22 36727359
    [Google Scholar]
  43. Wang W. Wang Q. Wan D. Sun Y. Wang L. Chen H. Liu C. Petersen R.B. Li J. Xue W. Zheng L. Huang K. Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy. Autophagy 2017 13 5 941 954 10.1080/15548627.2017.1293768 28409999
    [Google Scholar]
  44. Wei T.T. Zhang M.Y. Zheng X.H. Xie T.H. Wang W. Zou J. Li Y. Li H.Y. Cai J. Wang X. Tan J. Yang X. Yao Y. Zhu L. Interferon‐γ induces retinal pigment epithelial cell Ferroptosis by a JAK1‐2/STAT1/SLC7A11 signaling pathway in age‐related macular degeneration. FEBS J. 2022 289 7 1968 1983 10.1111/febs.16272 34741776
    [Google Scholar]
  45. Dhirachaikulpanich D. Li X. Porter L.F. Paraoan L. Integrated Microarray and RNAseq transcriptomic analysis of Retinal Pigment Epithelium/Choroid in age-related macular degeneration. Front. Cell Dev. Biol. 2020 8 808 10.3389/fcell.2020.00808 32984320
    [Google Scholar]
  46. Su Y. Yi Y. Li L. Chen C. circRNA-miRNA-mRNA network in age-related macular degeneration: From construction to identification. Exp. Eye Res. 2021 203 108427 10.1016/j.exer.2020.108427 33383027
    [Google Scholar]
  47. Choi Y.A. Jeong A. Woo C.H. Cha S.C. Park D.Y. Sagong M. Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing. Sci. Rep. 2023 13 1 1274 10.1038/s41598‑023‑28385‑7 36690666
    [Google Scholar]
/content/journals/cg/10.2174/0113892029291661241114055924
Loading
/content/journals/cg/10.2174/0113892029291661241114055924
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test