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Bioinformatics Analysis of MicroRNA Profiles Unveils Novel Biological Markers of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a degenerative neurological disease that mostly affects the elderly in numerous countries all over the world. The miRNA expression profile of GSE157239, as well as the gene expression profiles of GSE33000, GSE122063, and GSE118553, were used to identify differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between AD patients and healthy controls, with the objective of determining miRNAs involved in the pathogenesis of Alzheimer’s disease and recommending novel miRNA biomarkers in Alzheimer’s patients. The detected DEMs’ target genes were predicted using the mirTarBase and Tarbase databases and compared to the identified DEGs. Following that, 199 genes that overlapped between anticipated target genes from databases (mirTarBase and Tarbase) and discovered DEGs were approved as predicted target genes for DEMs. Funrich was also used to perform a Gene Ontology (GO) and pathway analysis for predicted target genes. Furthermore, the predicted target genes’ Protein–Protein Interaction (PPI) was displayed using the Cytoscape platform. PPI analysis revealed ten hub-genes of the target genes. As a consequence, 199 DEGs and 22 DEMs were revealed to be differently expressed between AD patients and healthy controls. Remarkably, type 2 diabetes was the pathway with the highest concentration of target genes. The link between diabetes and Alzheimer’s disease is thoroughly examined in the discussion section. Finally, the top detected DEMs among miRNAs were hsa-miR-125a-3p, hsa-miR-6131, hsa-miR-24-3p, hsa-miR-208a-5p, hsa-miR-6761-3p, and hsa-miR-3646. These findings significantly add to our understanding of the molecular pathways and associated miRNAs involved in the development of Alzheimer’s disease.

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REFERENCES

  1. Talwar, P., Silla, Y., Grover, S., Gupta, M., Agarwal, R., Kushwaha, S., and Kukreti, R., BMC Genomics, 2014, vol. 15, no. 1, p. 199.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kließ, M. K., Martins, R., and Connolly, M. P., J. Prev. Alzheimer’s Dis., 2021, vol. 8, no. 3, pp. 362–370.

    Google Scholar 

  3. Kotecha, A. M., Corrêa, A. D. C., Fisher, K. M., and Rushworth, J. V., Biosensors, 2018, vol. 8, no. 2., https://doi.org/10.3390/BIOS8020041

  4. Weuve, J., Hebert, L. E., Scherr, P. A., and Evans, D. A., Alzheimers. Dement., 2014, vol. 10, no. 2, p. e40.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Barnes, J., Dickerson, B. C., Frost, C., Jiskoot, L. C., Wolk, D., and Van Der Flier, W. M., Alzheimers. Dement., 2015, vol. 11, no. 11, pp. 1349–1357.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Colom-Cadena, M., Spires-Jones, T., Zetterberg, H., Blennow, K., Caggiano, A., DeKosky, S. T., Fillit, H., Harrison, J. E., Schneider, L. S, Scheltens, P., de Haan, W., Grundman, M., van Dyck, C. H., Izzo, N. J., Catalano, S. M., and the Synaptic Health Endpoints Working Group, Alzheimers. Res. Ther., 2020, vol. 12, no. 1, https://doi.org/10.1186/S13195-020-00588-4

  7. Westman, E., Aguilar, C., Muehlboeck, J. S., and Simmons, A., Brain Topogr., 2013, vol. 26, no. 1, pp. 9–23.

    Article  PubMed  Google Scholar 

  8. Memczak, S., Papavasileiou, P., Peters, O., and Rajewsky, N., PLoS One, 2015, vol. 10, no. 10, https://doi.org/10.1371/JOURNAL.PONE.0141214

  9. Hammond, S. M., 2015, Adv. Drug Deliv. Rev., vol. 87, pp. 3–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gebert, L. F. R. and MacRae, I. J., “Regulation of microRNA function in animals,” Nat. Rev. Mol. Cell Biol., 2018, vol. 20, no. 1, pp. 21–37.

    Article  Google Scholar 

  11. Lu, T. X. and Rothenberg, M. E., J. Allergy Clin. Immunol., 2018, vol. 141, no. 4, pp. 1202–1207.

    Article  CAS  PubMed  Google Scholar 

  12. Bekris, L. M., Yu, C. E., Bird, T. D., and Tsuang, D. W., J. Geriatr. Psychiatry Neurol., 2010, vol. 23, no. 4, pp. 213–227.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Karch, C. M., Jeng, A. T., Nowotny, P., Cady, J., Cruchaga, C., and Goate, A. M., PLoS One, 2012, vol. 7, no. 11, https://doi.org/10.1371/JOURNAL.PONE.0050976

  14. Dong, H., Lei, J., Ding, L., Wen, Y., Ju, H., and Zhang, X., Chem. Rev., 2013, vol. 113, no. 8, pp. 6207–6233.

    Article  CAS  PubMed  Google Scholar 

  15. Stappert, L. et al., PLoS One, 2013, vol. 8, no. 3, https://doi.org/10.1371/JOURNAL.PONE.0059011

  16. Ferrante, M. and Conti, G. O., MicroRNA, 2017., vol. 6, no. 3, https://doi.org/10.2174/2211536606666170811151503

  17. Kumar, P., Dezso, Z., MacKenzie, C., Oestreicher, J., Agoulnik, S., Byrne, M., Bernier, F., Yanagimachi, M., Aoshima, K., and Oda, Y., PLoS One, 2013, vol. 8, no. 7, p. e69807, https://doi.org/10.1371/JOURNAL.PONE.0069807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Femminella, G. D., Ferrara, N., and Rengo, G., Front. Physiol., 2015, vol. 6, no. FEB, p. 40, https://doi.org/10.3389/FPHYS.2015.00040/BIBTEX

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fransquet, P. D. and Ryan, J., Clin. Biochem., 2018, vol. 58, pp. 5–14.

    Article  CAS  PubMed  Google Scholar 

  20. Bekris, L. M., Lutz, F., Montine, T. J., Yu, C. E., Tsuang, D., Peskind, E. R. and Leverenz, J. B., Biomarkers, 2013, vol. 18, no. 5, pp. 455–466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kiko, T., Nakagawa, K., Tsuduki, T., Furukawa, K., Arai, H., and Miyazawa, T., J. Alzheimer’s Dis., 2014, vol. 39, no. 2, pp. 253–259.

    Article  CAS  Google Scholar 

  22. Zetterberg, H. and Burnham, S. C., Mol. Brain, 2019, vol. 12, no. 1, pp. 1–7.

    Article  CAS  Google Scholar 

  23. Cheng, L. et al., Mol. Psychiatry, 2014, vol. 20, no. 10, pp. 1188–1196.

    Article  PubMed  Google Scholar 

  24. Nagaraj, S. et al., Oncotarget, 2017, vol. 8, no. 10, pp. 16122–16143.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kalra, H., Drummen, G. P. C., and Mathivanan, S., Int. J. Mol. Sci., 2016, vol. 17, no. 2, https://doi.org/10.3390/IJMS17020170

  26. Barbagallo, C. et al., Cell. Mol. Neurobiol., 2020, vol. 40, no. 4, pp. 531–546.

    Article  CAS  PubMed  Google Scholar 

  27. Ren, L., Zhou, X., Huang, X., Wang, C., and Li, Y., Life Sci., 2019, vol. 217, pp. 229–236.

    Article  CAS  PubMed  Google Scholar 

  28. de la Monte, S. M., BMB Rep., 2009, vol. 42, no. 8, p. 475.

    Article  CAS  PubMed  Google Scholar 

  29. De Ferrari, G. V. and Inestrosa, N. C., Brain Res. Rev., 2000, vol. 33, no. 1, pp. 1–12.

    Article  CAS  PubMed  Google Scholar 

  30. Desale, S. E., and Chinnathambi, S., Cell Commun. Signal., 2021, vol. 19, no. 1, pp. 1–12.

    Article  Google Scholar 

  31. Uddin, M. S. et al., IUBMB Life, 2020, vol. 72, no. 9, pp. 1843–1855.

    Article  CAS  PubMed  Google Scholar 

  32. Sun, P. et al., Biosci. Rep., 2019, vol. 39, no. 1, p. 20180902.

    Article  Google Scholar 

  33. Singulani, M. P. et al., Exp. Gerontol., 2020, vol. 133, https://doi.org/10.1016/J.EXGER.2020.110882

  34. Rizzi, L. and Roriz-Cruz, M., Neuropeptides, 2018, vol. 71, pp. 54–60.

    Article  CAS  PubMed  Google Scholar 

  35. Cheng, Y., and Bai, F., Front. Neurosci., 2018, vol. 12, no. MAR, p. 163, https://doi.org/10.3389/FNINS.2018.00163/BIBTEX

    Article  PubMed  PubMed Central  Google Scholar 

  36. Choi, E. J., Son, Y. D., Noh, Y., Lee, H., Kim, Y. B., and Park, K. H., J. Clin. Neurol., 2018, vol. 14, no. 2, pp. 158–164.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kellar, D. and Craft, S., Lancet Neurol., 2020, vol. 19, no. 9, pp. 758–766.

    Article  CAS  PubMed  Google Scholar 

  38. Chang, W. et al., J. Agric. Food Chem., 2019. vol. 67, no. 27, pp. 7684–7693.

    Article  CAS  PubMed  Google Scholar 

  39. Femminella, G. D. et al., J. Diabetes Res., 2017, vol. 2017, https://doi.org/10.1155/2017/7420796

  40. Checler, F., Goiran, T., and Alves da Costa, C., Autophagy, 2018, vol. 14, no. 6, pp. 1099–1101.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Kowalska, M., Wize, K., Prendecki, M., Lianeri, M., Kozubski, W., and Dorszewska, J., Curr. Alzheimer Res., 2020, vol. 17, no. 3, pp. 208–223.

    Article  CAS  PubMed  Google Scholar 

  42. Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C., and Collin, F., Redox Biol., 2018, vol. 14, pp. 450–464.

    Article  CAS  PubMed  Google Scholar 

  43. Kim, J. K., Kim, T. S., Basu, J., and Jo, E. K., Cell. Microbiol., 2017, vol. 19, no. 1, p. e12687.

    Article  Google Scholar 

  44. Lopez-Ramirez, M. A., Reijerkerk, A., De Vries, H. E., and Romero, I. A., FASEB J., 2016,vol. 30, no. 8, pp. 2662–2672.

    Article  CAS  PubMed  Google Scholar 

  45. Yllmaz, Ş. G., Erdal, M. E., Özge, A. A., and Sungur, M. A., OMICS, 2016, vol. 20, no. 8, pp. 456–461.

    Article  Google Scholar 

  46. Aguilar, B. J., Zhu, Y., and Lu, Q., Alzheimer’s Res. Ther., 2017, vol. 9, no. 1, pp. 1–10.

    Article  Google Scholar 

  47. Mano, T. et al., Proc. Natl. Acad. Sci. U. S. A., 2017, vol. 114, no. 45, pp. E9645–E9654.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Ahmad, S. et al., Sci. Reports, 2020, vol. 10, no. 1, pp. 1–13.

    Google Scholar 

  49. Khan, R., Kadamkode, V., Kesharwani, D., Purkayastha, S., Banerjee, G., and Datta, M., RNA Biol., 2020, vol. 17, no. 2, pp. 188–201.

    Article  PubMed  Google Scholar 

  50. Lugli, G.et al., PLoS One, 2015, vol. 10, no. 10, p. e0139233.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Villa, C. et al., Rejuvenation Res., 2011, vol. 14, no. 3, pp. 275–281.

    Article  CAS  PubMed  Google Scholar 

  52. Sellers, K. J.et al., Alzheimer’s Dement., 2018, vol. 14, no. 3, p. 306, https://doi.org/10.1016/J.JALZ.2017.09.008

    Article  Google Scholar 

  53. Lin, F., Zhang, H., Bao, J., and Li, L., World Neurosurg., 2021, vol. 153, pp. e315–e328.

    Article  PubMed  Google Scholar 

  54. Liu, L., Liu, L., Lu, Y., Zhang, T., and Zhao, W., Biomark. Med., vol. 15, no. 16, pp. 1499–1507.

  55. Ji, Q., Wang, X., Cai, J., Du, X., Sun, H., and Zhang, N., 2019, Curr. Neurovasc. Res., vol. 16, no. 5, pp. 473–480.

    Article  CAS  PubMed  Google Scholar 

  56. Lee, H. G. et al., Am. J. Pathol., 2009, vol. 174, no. 3, p. 891, https://doi.org/10.2353/AJPATH.2009.080583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Woodbury, M. E. and Ikezu, T., J. Neuroimmune Pharmacol., 2014, vol. 9, no. 2, pp. 92–101.

    Article  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Islamic Azad University of science and research branch, Tehran, Iran

      Alireza Rahimpour

    2. Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

      Roozbeh Heidarzadehpilehrood

    3. Department of Computer Sciences, Kashmar Higher Education Institute, Kashmar, Iran

      Majid Aghel

    4. Trauma Research Center, Aja University of Medical Sciences, Tehran, Iran

      Zahra Jamalpoor

    5. Ahvaz Jundishapur University of Medical Sciences, Ahavz, Iran

      Parichehr Heydarian

    6. Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia

      Seyed Abbas Ghasemi

    7. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

      Maryam Pirhoushiaran

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    1. Alireza Rahimpour
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    Institutional Review Board Statement. This article does not contain any studies with human participants or animals performed by any of the authors.

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    Authors’ contributions. Alireza Rahimpour, Roozbeh Heidarzadehpilehrood, Majid Aghel, Zahra Jamalpoor, Parichehr Heydarian, Seyed Abbas Ghasemi, and Maryam Pirhoushiaran served as co-first authors on this study and contributed equally to the writing, reviewing, and editing. Maryam Pirhoushiaran served as project supervisor. All authors approved the final manuscript’s contents for publication.

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    Corresponding author; address: Department of Medical Genetics, Ground Floor, Building No. 8, School of Medicine, East Door, Tehran University of Medical Sciences, Ghods St., Enghelab St., Tehran, Iran; phone: +989190227143; е-mail: maryam.pirhoushiaran@gmail.com.

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    Rahimpour, A., Heidarzadehpilehrood, R., Aghel, M. et al. Bioinformatics Analysis of MicroRNA Profiles Unveils Novel Biological Markers of Alzheimer’s Disease. Neurochem. J. 16, 334–342 (2022). https://doi.org/10.1134/S1819712422030096

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