Reports of Biochemistry
and Molecular Biology
Thu, Nov 21, 2024
[Archive]
Volume 13, Issue 1 (Vol.13 No.1 Apr 2024)
rbmb.net 2024, 13(1): 1-12 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Jasim Tuama Ali S, Khalaj-Kondori M, Hoseinpour Feizi M A, Haghi M. Expression Levels of miR -124a, miR-545-3p and BDNF in the Peripheral Blood Mononuclear Cells Are Associated with the Severity of Autism. rbmb.net 2024; 13 (1) :1-12
URL: http://rbmb.net/article-1-1339-en.html
URL: http://rbmb.net/article-1-1339-en.html
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Abstract: (641 Views)
Background: People with autism frequently exhibit poor social skills, communication difficulties, and repetitive and stereotyped behaviors. MicroRNAs (miRNAs) are potential and promised targets in developing of new treatment strategies for autism.This study aimed to assess the relative expression of miR-124a, miR-34a-3p, miR-545-3p, miR-153, and BDNF in the blood samples of autistic children.
Methods: The children autism rating scale (CARS) was used to determine the severity of autism and to confirm the diagnosis. Blood samples were obtained from 50 patients and 40 age-/sex-matched healthy controls. Expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were evaluated using qRT-PCR. Pearson's correlation coefficient and regression analysis were used to check correlations between relative expressions of the miRNAs and BDNF. Biomarker potencies were assessed by ROC curve analysis.
Results: qRT-PCR analysis showed that the relative expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were significantly higher in the patients' group than the healthy controls. However, the relative expression of miR-153 was significantly lower in the case group than the control group. The relative expression of miR-124a was positively correlated with those of miR-545-3p and BDNF among the patients group. Also, the relative expressions of miR-545-3p and BDNF were positively correlated with each other. The ROC curve data also indicated that miR-124a, miR-34a-3p, miR-545-3p, miR-153, and BDNF could be possible diagnostic biomarker for CARS diagnosis (AUC=0.8328, AUC=0.8354, AUC=0.6727, AUC=0.8518 and AUC=0.8214, respectively).
Conclusions: Deregulation of miR-124a, miR-454-3p and BDNF might be considered as potential biomarkers for severity of autism.
Methods: The children autism rating scale (CARS) was used to determine the severity of autism and to confirm the diagnosis. Blood samples were obtained from 50 patients and 40 age-/sex-matched healthy controls. Expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were evaluated using qRT-PCR. Pearson's correlation coefficient and regression analysis were used to check correlations between relative expressions of the miRNAs and BDNF. Biomarker potencies were assessed by ROC curve analysis.
Results: qRT-PCR analysis showed that the relative expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were significantly higher in the patients' group than the healthy controls. However, the relative expression of miR-153 was significantly lower in the case group than the control group. The relative expression of miR-124a was positively correlated with those of miR-545-3p and BDNF among the patients group. Also, the relative expressions of miR-545-3p and BDNF were positively correlated with each other. The ROC curve data also indicated that miR-124a, miR-34a-3p, miR-545-3p, miR-153, and BDNF could be possible diagnostic biomarker for CARS diagnosis (AUC=0.8328, AUC=0.8354, AUC=0.6727, AUC=0.8518 and AUC=0.8214, respectively).
Conclusions: Deregulation of miR-124a, miR-454-3p and BDNF might be considered as potential biomarkers for severity of autism.
Keywords: Autistic children, Autism, Biomarker, Brain-derived neurotrophic factor, Gene expression, miRNA.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2024/02/6 | Accepted: 2024/03/21 | Published: 2024/10/22
Received: 2024/02/6 | Accepted: 2024/03/21 | Published: 2024/10/22
References
1. Khakzad MR, Javanbakht M, Shayegan MR, Kianoush S, Omid F, Hojati M, Meshkat M. The complementary role of high sensitivity C-reactive protein in the diagnosis and severity assessment of autism. Res Autism Spectr Disord. 2012;6(3):1032-7. [DOI:10.1016/j.rasd.2011.10.002]
2. Sayad A, Ghafouri-Fard S, Noroozi R, Omrani MD, Ganji M, Dastmalchi R, et al. Association Study of Sequence Variants in Voltage-gated Ca2+ Channel Subunit Alpha-1C and Autism Spectrum Disorders. Rep Biochem Mol Biol. 2019;8(1):56-62.
3. Sabbagh HJ, Al-Jabri BA, Alsulami MA, Hashem LA, Aljubour AA, Alamoudi RA. Prevalence and characteristics of autistic children attending autism centres in 2 major cities in Saudi Arabia: A cross-sectional study. Saudi Med J. 2021;42(4):419-27. [DOI:10.15537/smj.2021.42.4.20200630] [PMID] []
4. Guo X, Duan X, Chen H, He C, Xiao J, Han S, et al. Altered inter- and intrahemispheric functional connectivity dynamics in autistic children. Hum Brain Mapp. 2020;41(2):419-28. [DOI:10.1002/hbm.24812] [PMID] []
5. Khakzad MR, Salari F, Javanbakht M, Hojati M, Varasteh A, Sankian M, Meshkat M. Transforming Growth Factor Beta 1 869T/C and 915G/C Polymorphisms and Risk of Autism Spectrum Disorders. Rep Biochem Mol Biol. 2015;3(2):82-8.
6. Khakzad MR, Javanbakht M, Soltanifar A, Hojati M, Delgosha M, Meshkat M. The Evaluation of Food Allergy on Behavior in Autistic Children. Rep Biochem Mol Biol. 2012;1(1):37-42.
7. Yang W, Liu M, Zhang Q, Zhang J, Chen J, Chen Q, Suo L. Knockdown of miR-124 Reduces Depression-like Behavior by Targeting CREB1 and BDNF. Curr Neurovasc Res. 2020;17(2):196-203. [DOI:10.2174/1567202617666200319141755] [PMID] []
8. Zhang J, Liu L, Xu T, Zhang W, Zhao C, Li S, et al. Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data. BMC bioinformatics. 2021;22(1):578. [DOI:10.1186/s12859-021-04498-6] [PMID] []
9. Gruzdev SK, Yakovlev AA, Druzhkova TA, Guekht AB, Gulyaeva NV. The Missing Link: How Exosomes and miRNAs can Help in Bridging Psychiatry and Molecular Biology in the Context of Depression, Bipolar Disorder and Schizophrenia. Cell Mol Neurobiol. 2019;39(6):729-50. [DOI:10.1007/s10571-019-00684-6] [PMID]
10. Hicks SD, Carpenter RL, Wagner KE, Pauley R, Barros M, Tierney-Aves C, et al. Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development. J Am Acad Child Adolesc Psychiatry. 2020;59(2):296-308. [DOI:10.1016/j.jaac.2019.03.017] [PMID] []
11. Wu X, Li W, Zheng Y. Recent Progress on Relevant microRNAs in Autism Spectrum Disorders. Int J Mol Sci. 2020;21(16):5904. [DOI:10.3390/ijms21165904] [PMID] []
12. Chaya T, Maeda Y, Sugimura R, Okuzaki D, Watanabe S, Varner LR, et al. Multiple knockout mouse and embryonic stem cell models reveal the role of miR-124a in neuronal maturation. J Biol Chem. 2022;298(9):102293. [DOI:10.1016/j.jbc.2022.102293] [PMID] []
13. Yang L, Zhu Y, Kong D, Gong J, Yu W, Liang Y, et al. EGF suppresses the expression of miR-124a in pancreatic β cell lines via ETS2 activation through the MEK and PI3K signaling pathways. Int J Biol Sci. 2019;15(12):2561-75. [DOI:10.7150/ijbs.34985] [PMID] []
14. Rao VTS, Fuh SC, Karamchandani JR, Woulfe JMJ, Munoz DG, Ellezam B, et al. Astrocytes in the Pathogenesis of Multiple Sclerosis: An In Situ MicroRNA Study. J Neuropathol Exp Neurol. 2019;78(12):1130-46. [DOI:10.1093/jnen/nlz098] [PMID]
15. Wegner S, Uhlemann R, Boujon V, Ersoy B, Endres M, Kronenberg G, Gertz K. Endothelial Cell-Specific Transcriptome Reveals Signature of Chronic Stress Related to Worse Outcome After Mild Transient Brain Ischemia in Mice. Mol Neurobiol. 2020;57(3):1446-58. [DOI:10.1007/s12035-019-01822-3] [PMID] []
16. Li J, Xu X, Liu J, Zhang S, Tan X, Li Z, et al. Decoding microRNAs in autism spectrum disorder. Mol Ther Nucleic Acids. 2022;30:535-46. [DOI:10.1016/j.omtn.2022.11.005] [PMID] []
17. Araghi-Niknam M, Fatemi SH. Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. Cell Mol Neurobiol. 2003;23(6):945-52. [DOI:10.1023/B:CEMN.0000005322.27203.73] [PMID]
18. Shen J, Su X, Wang Q, Ke Y, Zheng T, Mao Y, et al. Current and future perspectives on the regulation and functions of miR-545 in cancer development. Cancer Pathog Ther. 2023.
https://doi.org/10.1016/j.cpt.2023.09.001 [DOI:10.1016/j.cpt.2023.09.001.] [PMID] []
19. Cosín-Tomás M, Antonell A, Lladó A, Alcolea D, Fortea J, Ezquerra M, et al. Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer's Disease: Potential and Limitations. Mol Neurobiol. 2017;54(7):5550-62. [DOI:10.1007/s12035-016-0088-8] [PMID]
20. Kalemaj Z, Marino MM, Santini AC, Tomaselli G, Auti A, Cagetti MG, et al. Salivary microRNA profiling dysregulation in autism spectrum disorder: A pilot study. Front Neurosci. 2022;16:945278. [DOI:10.3389/fnins.2022.945278] [PMID] []
21. Jaberi KR, Alamdari-Palangi V, Jaberi AR, Esmaeli Z, Shakeri A, Gheibi Hayat SM, et al. The Regulation, Functions, and Signaling of miR-153 in Neurological Disorders, and Its Potential as a Biomarker and Therapeutic Target. Curr Mol Med. 2023;23(9):863-75. [DOI:10.2174/1566524023666220817145638] [PMID]
22. You YH, Qin ZQ, Zhang HL, Yuan ZH, Yu X. MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR. Biosci Rep. 2019;39(6) :BSR20181904. [DOI:10.1042/BSR20181904] [PMID] []
23. Halepoto DM, Bashir S, L ALA. Possible role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder: current status. J Coll Physicians Surg Pak. 2014;24(4):274-8.
24. Jebelli A, Khalaj-Kondori M, Bonyadi M, Hosseinpour Feizi MA, Rahmati-Yamchi M. Beta-Boswellic Acid and Ethanolic Extract of Olibanum Regulating the Expression Levels of CREB-1 and CREB-2 Genes. Iran J Pharm Res. 2019;18(2):877-86.
25. Khalaj-Kondori M, Sadeghi F, Hosseinpourfeizi MA, Shaikhzadeh-Hesari F, Nakhlband A, Rahmati-Yamchi M. Boswellia serrata gum resin aqueous extract upregulatesBDNF but not CREB expression in adult male rat hippocampus. Turk J Med Sci. 2016;46(5):1573-8. [DOI:10.3906/sag-1503-43] [PMID]
26. Sikandar S, Minett MS, Millet Q, Santana-Varela S, Lau J, Wood JN, Zhao J. Brain-derived neurotrophic factor derived from sensory neurons plays a critical role in chronic pain. Brain. 2018;141(4):1028-39. [DOI:10.1093/brain/awy009] [PMID] []
27. Bryn V, Halvorsen B, Ueland T, Isaksen J, Kolkova K, Ravn K, Skjeldal OH. Brain derived neurotrophic factor (BDNF) and autism spectrum disorders (ASD) in childhood. Eur J Paediatr Neurol. 2015;19(4):411-4. [DOI:10.1016/j.ejpn.2015.03.005] [PMID]
28. Genovese A, Butler MG. The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations. Genes. 2023;14(3):677. [DOI:10.3390/genes14030677] [PMID] []
29. Xie S, Karlsson H, Dalman C, Widman L, Rai D, Gardner RM, et al. The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability. Autism Res. 2020;13(12):2242-50. [DOI:10.1002/aur.2417] [PMID] []
30. Abdelrahman AH, Eid OM, Ibrahim MH, Abd El-Fattah SN, Eid MM, Meguid NA. Evaluation of circulating miRNAs and mRNAs expression patterns in autism spectrum disorder. Egypt J Med Hum Genet. 2021;22(81):1-10. [DOI:10.1186/s43042-021-00202-8]
31. Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009;12(4):399-408. [DOI:10.1038/nn.2294] [PMID] []
32. Zhang Y, Pang Y, Feng W, Jin Y, Chen S, Ding S, et al. miR-124 regulates early isolation-induced social abnormalities via inhibiting myelinogenesis in the medial prefrontal cortex. Cell Mol Life Sci. 2022;79(9):507. [DOI:10.1007/s00018-022-04533-6] [PMID]
33. Choi SY, Pang K, Kim JY, Ryu JR, Kang H, Liu Z, et al. Post-transcriptional regulation of SHANK3 expression by microRNAs related to multiple neuropsychiatric disorders. Mol Brain. 2015;8(1):74.
https://doi.org/10.1186/s13041-015-0165-3 [DOI:10.1186/s13041-018-0415-2] [PMID] []
34. Araghi-Niknam M, Fatemi SH. Levels of Bcl-2 and P53 Are Altered in Superior Frontal and Cerebellar Cortices of Autistic Subjects. Cell Mol Neurobiol. 2003;23(6):945-52. [DOI:10.1023/B:CEMN.0000005322.27203.73] [PMID]
35. Kim AH, Reimers M, Maher B, Williamson V, McMichael O, McClay JL, et al. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res. 2010;124(1-3):183-91. [DOI:10.1016/j.schres.2010.07.002] [PMID] []
36. Rizzuti M, Melzi V, Gagliardi D, Resnati D, Meneri M, Dioni L, et al. Insights into the identification of a molecular signature for amyotrophic lateral sclerosis exploiting integrated microRNA profiling of iPSC-derived motor neurons and exosomes. Cell Mol Life Sci. 2022;79(3):189. [DOI:10.1007/s00018-022-04217-1] [PMID] []
37. Fyfe I. MicroRNAs - diagnostic markers in Parkinson disease? Nat Rev Neurol. 2020;16(2):65.
https://doi.org/10.1038/s41582-019-0305-y [DOI:10.1038/s41582-021-00604-7] [PMID]
38. Wang M, Qin L, Tang B. MicroRNAs in Alzheimer's Disease. Front in genetics. 2019;10:153. [DOI:10.3389/fgene.2019.00153] [PMID] []
39. Barbosa AG, Pratesi R, Paz GSC, dos Santos MAAL, Uenishi RH, Nakano EY, et al. Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder. Sci Rep. 2020;10(1):17348. [DOI:10.1038/s41598-020-74239-x] [PMID] []
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
