Allium sativum'a Özgü Ast-miR2 MikroRNA’sının PCDH19 Gen Ekspresyonu Üzerine Etkisi: Epilepside Olumsuz Bir Türler Arası (Cross-Kingdom) Etkileşim
Abstract
Epilepsi, yaşamın ilk yılında ve ileri yaşlarda yüksek insidans gösteren, en yaygın üçüncü nörolojik hastalıktır. Hastaların yaklaşık üçte birinde ilaçlara dirençli nöbetler görülmekte olup bu durum alternatif tedavilere olan ilgiyi artırmaktadır. Bitki ve gıdalardan türetilen mikroRNA’ların (miRNA) “türler arası düzenleme” yoluyla memeli gen ekspresyonunu düzenleyebildiği gösterilmiştir. Bitkisel tedaviler arasında Allium sativum (sarımsak) öne çıkmakta olup, altı potansiyel miRNA (Ast-miR1–Ast-miR6) tanımlanmıştır. Bu çalışmada, A. sativum kökenli miRNA’ların epilepsi ile ilişkili hedefleri in silico araçlarla (psRNATarget, NCBI, OMIM) belirlenmiştir. Ast-miR2, Ast-miR3 ve Ast-miR5’in sırasıyla PCDH19, SLC6A1 ve CNTN2 üzerindeki etkileri SH-SY5Y hücrelerinde değerlendirilmiştir. Ast-miR2 mimik transfeksiyonu, kontrol grubuna kıyasla PCDH19 ekspresyonunu anlamlı düzeyde azaltmış (Katlanma Değişimi [FC] = 0,07) ve hücre canlılığını %13 düşürmüştür (%87 canlılık, p < 0,05). Buna karşılık, Ast-miR3 ve Ast-miR5 transfeksiyonlarının ardından SLC6A1 (FC = 1,08, p = 0,12) veya CNTN2 (FC = 1,16, p = 0,09) ekspresyonunda anlamlı bir değişiklik gözlenmemiştir. Bu bulgular, Ast-miR2 ile PCDH19 arasındaki potansiyel olumsuz etkileşimin epilepsi patogenezine katkıda bulunabileceğini düşündürmektedir. Türler arası miRNA düzenlemesinin epilepsideki terapötik veya olumsuz etkilerini netleştirmek için ileri çalışmalara ihtiyaç vardır.
Keywords
Allium sativum Ast-miR2 PCDH19 epilepsi türler arası düzenleme bitki kökenli miRNA mikroRNA taklidi (mimik)
Project Number
T-2022-899
References
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Effect of Allium sativum-Derived Ast-miR2 microRNA on PCDH19 Gene Expression: A Negative Cross-Kingdom Interaction in Epilepsy
Abstract
Epilepsy is the third most common neurological disorder, with high incidence in the first year of life and later decades. About one-third of patients have drug-resistant seizures, prompting interest in alternative therapies. Plant- and food-derived microRNAs (miRNAs) can regulate mammalian gene expression through “cross-kingdom regulation.” Among herbal treatments, Allium sativum (garlic) is notable, with six potential miRNAs (Ast-miR1–Ast-miR6) identified. This study used in silico tools (psRNATarget, NCBI, OMIM) to identify epilepsy-related targets for A. sativum-derived miRNAs. The effects of Ast-miR2, Ast-miR3, and Ast-miR5 on their respective targets—PCDH19, SLC6A1, and CNTN2—were evaluated in SH-SY5Y cells. Ast-miR2 mimic transfection significantly reduced PCDH19 expression compared to controls (Fold Change [FC] = 0.07) and decreased cell viability by 13% (87% viability, p < 0.05). No significant changes were observed in SLC6A1 (FC = 1.08, p = 0.12) or CNTN2 (FC = 1.16, p = 0.09) expression after Ast-miR3 and Ast-miR5 transfection, respectively. These findings suggest a potential detrimental interaction between Ast-miR2 and PCDH19, which may contribute to epilepsy pathogenesis. Further studies are needed to clarify the therapeutic or adverse implications of cross-kingdom miRNA regulation in epilepsy.
Supporting Institution
Sivas Cumhuriyet University Scientific Research Projects Unit
Project Number
T-2022-899
References
- 1. Zhang L, Hou D, Chen X, et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012; 22: 107–26.
- 2. Saumet A, Lecellier CH. Anti-viral RNA silencing: do we look like plants?. Retrovirology. 2006; 3: 3. https://doi.org/10.1186/1742-4690-3-3
- 3. Zhang B, Pan X, Stellwag EJ. Identification of soybean microRNAs and their targets. Planta. 2008; 229(1): 161–82. https://doi.org/10.1007/s00425-008-0818-x
- 4. Jin W, Li N, Zhang B, et al. Identification and verification of microRNA in wheat (Triticum aestivum). Journal of plant research. 2008; 121(3): 351–5. https://doi.org/10.1007/s10265-007-0139-3
- 5. Xie F, Frazier TP, Zhang B. Identification, characterization and expression analysis of MicroRNAs and their targets in the potato (Solanum tuberosum). Gene. 2011; 473(1): 8–22. https://doi.org/10.1016/j.gene.2010.09.007
- 6. Panda D, Dehury B, Sahu J, et al. Computational identification and characterization of conserved miRNAsand their target genes in garlic (Allium sativum L.) expressedsequence tags. Gene. 2014; 537: 333-42.
- 7. Zhang B, Wang Q, Wang K, et al. Identification of cotton microRNAs and their targets. Gene. 2007; 397(1-2): 26–37. https://doi.org/10.1016/j.gene.2007.03.020
- 8. Ivashuta SI, Petrick JS, Heisel SE, et al. Endogenous small RNAs in grain: semi-quantification and sequence homology to human and animal genes. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2009; 47(2): 353–60. https://doi.org/10.1016/j.fct.2008.11.025
- 9. Liu YC, Chen WL, Kung WH, et al. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC genomics. 2017; 18(2): 112. https://doi.org/10.1186/s12864-017-3502-3
- 10. Jiang M, Sang X, Hong Z. Beyond nutrients: food-derived microRNAs provide cross-kingdom regulation. BioEssays: news and reviews in molecular, cellular and developmental biology. 2012; 34(4): 280–284. https://doi.org/10.1002/bies.201100181
- 11. Kosaka N, Izumi H, Sekine K, et al. microRNA as a new immune-regulatory agent in breast milk. Silence. 2010; 1(1): 7. https://doi.org/10.1186/1758-907X-1-7
- 12. Chen X, Gao C, Li H, et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res. 2010; 20: 1128–37.
- 13. Ergün S. Cross-Kingdom Gene regulation via miRNAs of Hypericum perforatum (St. John’s wort) flower dietetically absorbed: An in silico approach to define potential biomarkers for prostate cancer. Computational biology and chemistry. 2019; 80. https://doi.org/10.1016/j.compbiolchem.2019.02.010
- 14. Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS genetics. 2009; 5(2): e1000381. https://doi.org/10.1371/journal.pgen.1000381
- 15. Samanta D. PCDH19-Related Epilepsy Syndrome: A Comprehensive Clinical Review. Pediatric neurology. 2020; 105: 3–9. https://doi.org/10.1016/j.pediatrneurol.2019.10.009
- 16. Kowkabi S, Yavarian M, Kaboodkhani R, et al. PCDH19-clustering epilepsy, pathophysiology and clinical significance. Epilepsy & behavior: E&B. 2024; 154: 109730. https://doi.org/10.1016/j.yebeh.2024.109730
- 17. Hynes K, Tarpey P, Dibbens LM, et al. Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families. J Med Genet. 2010; 47: 211–6.
- 18. Dibbens LM, Tarpey PS, Hynes K, et al. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nature Genetics. 2008; 40(6): 776–81.
Details
| Primary Language | English |
|---|---|
| Subjects | Health and Community Services |
| Journal Section | Research Article |
| Authors | |
| Project Number | T-2022-899 |
| Publication Date | September 30, 2025 |
| Submission Date | August 18, 2025 |
| Acceptance Date | September 12, 2025 |
| Published in Issue | Year 2025 Volume: 47 Issue: 3 |
