Determination of miRNA Expression Levels Involved in WNT Signaling Pathway in Multiple Sclerosis Patients

Yıl 2022, Cilt: 3 Sayı: 1, 43 - 48, 15.01.2022

Ezgi Yaşar Eda Balkan Nuray Bilge

Öz

Background: Multiple Sclerosis (MS) is an autoimmune central nervous system disease characterized by inflammation, demyelination, and axon damage. Recent studies have shown that the WNT signaling pathway is a negative factor in the myelination process. miRNAs are non-protein-coding RNAs that play a role in processes such as cell development, differentiation, proliferation, and cell death by repressing target genes. As with many pathways, miRNAs are also effective in regulating the WNT signaling pathway. In our study, the expression levels of miRNAs (miR-145, miR-301b, miR214, miR-190a, miR-1304) targeting genes involved in the WNT signaling pathway were examined. Our study was carried out in order to comprehend the relationship between MS and the WNT signaling pathway, to contribute to the clinic and the literature in elucidating the etiology of MS, and determining treatment strategies with the results to be obtained.
Methods: Blood samples were taken from patients with MS (17) included in our study during both attack and remission periods. Blood samples were taken from the control group (16) participating in the study, and the expression levels of miRNAs included in our study were quantitatively analyzed using the RT-PCR method.
Results: When compared with the control group, no statistically significant difference was observed in terms of fold increase values in the miRNA levels (miR-145, miR-301b, miR-214, miR-190a ve miR-1304) of the MS attack period, while statistically significant differences (respectively; p=0.010, p=0.023, p=0.002, p=0.006, p=0.003) were found in terms of fold increase values of all miRNA levels in the remission period. Considering the medications used by the patients and the number of attacks, there was no statistically significant difference in miRNA expression levels.
Conclusion: In our study, it was deduced that miRNA expression levels, which are effective in the WNT signaling pathway, may play a role in elucidating the clinical course and genetic mechanism of MS, particularly during the remission period.

Anahtar Kelimeler

miRNA, multiple sclerosis, WNT signaling pathway

Destekleyen Kurum

ATATURK UNI BAP

Proje Numarası

2019-6949

Kaynakça

• Goldenberg MM. Multiple sclerosis review. P T, 2012, 37: 175-184.
• Jia L. Song , Priya Nigam, Senel S. Tektas et al. MicroRNA regulation of Wnt signaling pathways in development and disease. Cell Signal. 2015 ; 27(7): 1380–1391.
• Hitit M, Kurar E, Güzeloğlu A. Atatürk Üniversitesi Vet. Bil. Derg. 2015; 10(3): 211-218
• Xie C, Li Z, Zhang GX, Guan Y. Wnt signaling in remyelination in multiple sclerosis: friend or foe? Mol Neurobiol, 2014, 49: 1117-1125.
• Goldschmidt T, Antel J, Konig FB, Bruck W, Kuhlmann T. Remyelination capacity of the MS brain decreases with disease chronicity. Neurology, 2009, 72: 1914-1921.
• Stadelmann C, Bruck W. Interplay between mechanisms of damage and repair in multiple sclerosis. J Neurol, 2008, 255 1: 12-18
• Sinnecker T, Mittelstaedt P, Dorr J, Pfueller CF, Harms L, Niendorf T, Paul F, Wuerfel J. Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study. Arch Neurol, 2012, 69: 739-745 Saridas F. Investigation of miRNAs associated with Multiple Sclerosis development. Neurology. Bursa: Uludag University, 2018.
• de Faria O, Jr., Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS. MicroRNA dysregulation in multiple sclerosis. Front Genet, 2012, 3: 3
• Gandhi R, Healy B, Gholipour T,et al. Circulating microRNAs as biomarkers for disease staging in Multiple sclerosis. Annals of Neurology, 2013, 73: 729-740.
• Keller A, Leidinger P, Lange J, et al.. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One, 2009, 4: e7440
• Sondergaard HB, Hesse D, Krakauer M, Sorensen PS, Sellebjerg F. Differential microRNA expression in blood in multiple sclerosis. Mult Scler, 2013, 19: 1849- 1857
• Lopez-Ramirez MA, Reijerkerk A, de Vries HE, Romero IA. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation. FASEB J, 2016, 30: 2662-2672.
• Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH, Barres BA. Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination. Cell, 2009, 138: 172-185 . Huang L, Wang X, Zou J, Li J, Lu Q. Dysregulation of miR-1304-3p in hippocampus and serum of patients with intractable epilepsy. International Journal of Clinical and Experimental Pathology, 2017, 10: 4263-4272
• Hecker M, Thamilarasan M, Koczan D, Schroder I, Flechtner K, Freiesleben S, Fullen G, Thiesen HJ, Zettl UK. MicroRNA expression changes during interferonbeta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci, 2013, 14: 16087-16110.
• Singh J, Deshpande M, Suhail H, Rattan R, Giri S. Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response. J Neuroimmune Pharmacol, 2016, 11: 84-97.