Abstract
Vitamin D has been vastly acknowledged as a neuroactive steroid controlling neurodevelopment. As it exerts its functions through activation of vitamin D receptor (VDR), several studies have assessed the role of VDR in brain function. More recently, a number of long non-coding RNAs (lncRNAs) have been recognized that alter expression of VDR. In the current study, we evaluated expression of four VDR-related lncRNAs (LINC00511, LINC00346, SNHG6 and SNHG16) in peripheral blood of 40 epileptic patients and 39 healthy subjects using quantitative real time PCR method. The relative expression levels of SNHG16 and LINC00511 were higher in epileptic patients compared with healthy subjects. For SNHG16, the difference was only significant between male patients and male controls, while LINC00511 had the opposite pattern. The results of Quantile regression model showed significant associations between SNHG6 and SNHG16 expressions and gender (P values of 0.027 and 0.009 respectively). Significant correlations were detected between expression levels of SNHG6 and SNHG16 (r = 0.32, P = 0.004), SNHG6 and LINC00346 (r = 0.37, P = 0.001), SNHG16 and LINC00346 (r = 0.30, P = 0.007) as well as SNHG16 and LINC00511 (r = 0.29, P = 0.009). Expression of LINC00346 was inversely correlated with vitamin D levels only in male epileptic patients (r = −0.58, P = 0.011). Expression of SNHG6 was correlated with vitamin D levels in male controls but no other subgroups (r = 0.51, P = 0.044). Based on the results of ROC curve analysis, SNHG16 had the diagnostic power of 0.86 in male subjects. Taken together, the current study provides evidences for dys-regulation of VDR-related lncRNAs in epileptic patients. The clinical significance of these finding should be explored in future studies.
Similar content being viewed by others
References
Cai C, Huo Q, Wang X, Chen B, Yang Q (2017) SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem Biophys Res Commun 485:272–278
Groves NJ, McGrath JJ, Burne TH (2014) Vitamin D as a neurosteroid affecting the developing and adult brain. Annu Rev Nutr 34:117–141
He J, Zhang JF, Yi C, Lv Q, Xie WD, Li JN, Wan G, Cui K, Kung HF, Yang J, Yang BB, Zhang YO (2010) miRNA-mediated functional changes through co-regulating function related genes. PLoS One 5:e13558
Hollo A, Clemens Z, Kamondi A, Lakatos P, Szucs A (2012) Correction of vitamin D deficiency improves seizure control in epilepsy: a pilot study. Epilepsy Behav 24:131–133
Irani M, Seifer DB, Grazi RV, Irani S, Rosenwaks Z, Tal R (2017) Vitamin D decreases serum VEGF correlating with clinical improvement in vitamin D-deficient women with PCOS: a randomized placebo-controlled trial. Nutrients 9
Jiang P, Zhu WY, He X, Tang MM, Dang RL, Li HD, Xue Y, Zhang LH, Wu YQ, Cao LJ (2015) Association between vitamin D receptor gene polymorphisms with childhood temporal lobe epilepsy. Int J Environ Res Public Health 12:13913–13922
Kalueff AV, Minasyan A, Keisala T, Kuuslahti M, Miettinen S, Tuohimaa P (2006) Increased severity of chemically induced seizures in mice with partially deleted vitamin D receptor gene. Neurosci Lett 394:69–73
Karsten SL, Kudo LC, Bragin AJ (2011) Use of peripheral blood transcriptome biomarkers for epilepsy prediction. Neurosci Lett 497:213–217
Kholghi Oskooei V, Geranpayeh L, Omrani MD, Ghafouri-Fard S (2018) Assessment of functional variants and expression of long noncoding RNAs in vitamin D receptor signaling in breast cancer. Cancer Manag Res 10:3451–3462
Lu L, Qiu J, Liu S, Luo W (2008) Vitamin D3 analogue EB1089 inhibits the proliferation of human laryngeal squamous carcinoma cells via p57. Mol Cancer Ther 7:1268–1274
Mazdeh M, Ghafouri-Fard S, Hatami M, Eftekharian MM, Ganji M, Sayad A, Arsang-Jang S, Taheri M, Omrani MD (2018) Expression analysis of vitamin D signaling pathway genes in epileptic patients. J Mol Neurosci 64:551–558
Meier C, Kraenzlin ME (2011) Antiepileptics and bone health. Ther Adv Musculoskelet Dis 3:235–243
Ng SY, Lin L, Soh BS, Stanton LW (2013) Long noncoding RNAs in development and disease of the central nervous system. Trends Genet 29:461–468
Pendo K, Degiorgio CM (2016) Vitamin D3 for the treatment of epilepsy: basic mechanisms, animal models, and clinical trials. Front Neurol 7:218
Peng X, Vaishnav A, Murillo G, Alimirah F, Torres KE, Mehta RG (2010) Protection against cellular stress by 25-hydroxyvitamin D3 in breast epithelial cells. J Cell Biochem 110:1324–1333
Phabphal K, Geater A (2013) The association between BsmI polymorphism and risk factors for atherosclerosis in patients with epilepsy taking valproate. Seizure 22:692–697
Reynolds EH (1975) Chronic antiepileptic toxicity: a review. Epilepsia 16:319–352
Shimada T, Takemiya T, Sugiura H, Yamagata K (2014) Role of inflammatory mediators in the pathogenesis of epilepsy. Mediat Inflamm 2014:1–8
Ting HJ, Messing J, Yasmin-Karim S, Lee YF (2013) Identification of microRNA-98 as a therapeutic target inhibiting prostate Cancer growth and a biomarker induced by vitamin D. J Biol Chem 288:1–9
Vahid KO, Soudeh GF, Davood OM (2018) A combined bioinformatics and literature based approach for identification of long non-coding RNAs that modulate vitamin D receptor signaling in breast cancer. Klin Onkol 31:264–269
Wang W, Lou C, Gao J, Zhang X, Du Y (2018) LncRNA SNHG16 reverses the effects of miR-15a/16 on LPS-induced inflammatory pathway. Biomed Pharmacother 106:1661–1667
Yang BY, Meng Q, Sun Y, Gao L, Yang JX (2018) Long non-coding RNA SNHG16 contributes to glioma malignancy by competitively binding miR-20a-5p with E2F1. J Biol Regul Homeost Agents 32:251–261
Zhao X, Liu Y, Li Z, Zheng S, Wang Z, Li W, Bi Z, Li L, Jiang Y, Luo Y, Lin Q, Fu Z, Rufu C (2018) Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa-miR-29b-3p in pancreatic ductal adenocarcinoma. J Cell Mol Med 22:655–667
Zitman-Gal T, Green J, Pasmanik-Chor M, Golan E, Bernheim J, Benchetrit S (2014) Vitamin D manipulates miR-181c, miR-20b and miR-15a in human umbilical vein endothelial cells exposed to a diabetic-like environment. Cardiovasc Diabetol 13:8
Acknowledgements
The current study was supported by a grant from Hamadan University of Medical Sciences.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 190 kb)
Rights and permissions
About this article
Cite this article
Mazdeh, M., Zamani, M., Eftekharian, M.M. et al. Expression analysis of vitamin D receptor-associated lncRNAs in epileptic patients. Metab Brain Dis 34, 1457–1465 (2019). https://doi.org/10.1007/s11011-019-00446-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-019-00446-9