Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the pathogenesis of neuropsychiatric disorders such as epilepsy. In the current study, we evaluated expression of eight lncRNAs in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal individual using quantitative real-time PCR. Bayesian regression model showed significant higher expression of UCA1 in both refractory and non-refractory groups compared with controls (posterior beta of relative expression (RE) = 2.03, P value = 0.003, and posterior beta of RE = 4.05, P value < 0.0001, respectively). Besides, expression of UCA1 was higher in non-refractory patients compared with refractory ones (posterior beta of RE = 2.008, P value = 0.019). When repeating statistical analyses in a gender-based manner, differences in expression of UCA1 were significant in all subgroup analyses except for male non-refractory vs. refractory subgroups analysis. Expression levels of NKILA and ANRIL were higher in both refractory and non-refractory groups compared with controls (posterior beta of RE = 1.565, P value = 0.018, and posterior beta of RE = 1.902, P value = 0.006 for NKILA; posterior beta of RE = 1.304, P value < 0.0001, and posterior beta of RE = 1.603, P value = 0.019 for ANRIL, respectively). However, expression levels of these two lncRNAs were not different between refractory and non-refractory groups. Gender-based analysis for these two lncRNAs revealed similar results except for lack of difference in ANRIL expression between male refractory group and controls. Expression of THRIL was significantly lower in both refractory and non-refractory groups compared with controls (posterior beta of RE = − 0.842, P value = 0.044 and posterior beta of RE = − 1.969, P value < 0.0001, respectively). Furthermore, expression of this lncRNA was lower in non-refractory patients compared with refractory ones (posterior beta of RE = − 1.129, P value = 0.002). However, no significant difference was detected between non-refractory and refractory patients either in males or females. The interactions between gender and relative expressions of PACER, DILC, and MALAT1 were significant, so the results were assessed in gender-based manner. In females, expression of DILC was higher in non-refractory patients compared with refractory ones (posterior beta of RE = 0.959, P value = 0.044). Expression of MALAT1 was lower in female non-refractory patients compared with controls and in female non-refractory patients compared with refractory ones (posterior beta of RE = − 1.35, P value = 0.002, and posterior beta of RE = − 0.942, P value = 0.045, respectively). Finally, expression of PACER was higher in refractory patients vs. controls and non-refractory patients vs. controls in both male and female subgroups. However, comparison between non-refractory and refractory patients revealed significant results only among females. Expression of none of the assessed lncRNAs was correlated with age of study participants. There were robust correlations between expression levels of lncRNAs. The most robust correlations were detected between UCA1 and PACER (r = 0.84, P < 0.0001) and between UCA1 and ANRIL (r = 0.75, P < 0.0001). Taken together, our study demonstrated dysregulation of lncRNAs in peripheral blood of epileptic patients and potentiated them as biomarkers for this neurologic condition.

中文翻译：

---

lncRNA在难治性和非难治性癫痫患者中的表达分析

长的非编码RNA（lncRNA）已被证明参与神经精神疾病如癫痫病的发病机理。在本研究中，我们使用定量实时PCR评估了80例癫痫患者（40例难治性和40例非难治性患者）和40例正常个体中8种lncRNA的表达。贝叶斯回归模型显示UCA1在难治性和非难治性组中均显着高于对照组（相对表达的后beta（RE）= 2.03，P值= 0.003，RE的后β= 4.05，P值<0.0001，分别）。此外，UCA1在非难治患者中的表达高于难治性患者（RE的后β= 2.008，P值= 0.019）。当以性别为基础的方式重复进行统计分析时，UCA1表达的差异在所有亚组分析中均显着，除了男性非难治性和难治性亚组分析外。的表达水平NKILA和ANRIL分别与对照组相比在这两个耐火和非耐火组高（RE = 1.565，后路的β P值= 0.018，和RE = 1.902，后路的β P为值= 0.006 NKILA ;的后测试RE = 1.304，P值<0.0001，和RE = 1.603的后测试，P为值= 0.019 ANRIL， 分别）。但是，这两个lncRNA的表达水平在难治性和非难治性组之间没有差异。对这两个lncRNA的基于性别的分析显示了相似的结果，只是在男性难治组和对照组之间的ANRIL表达缺乏差异。与对照相比，难治性和非难治性组中THRIL的表达均显着降低（RE的后β=-0.842，P值= 0.044和RE的后β= = 1.969，P值<0.0001）。此外，与难治性患者相比，非难治性患者该lncRNA的表达更低（RE的后β= 1.129，P值= 0.002）。然而，在男性或女性的非难治性和难治性患者之间未检测到显着差异。性别与PACER，DILC和MALAT1的相对表达之间的相互作用非常显着，因此以基于性别的方式评估结果。在女性中，非难治性患者的DILC表达高于难治性患者（RE的后β= 0.959，P值= 0.044）。女性非难治性患者的MALAT1的表达低于对照组，女性非难治性患者的MALAT1的表达低于难治性的患者（RE的后β= 1.35，P值= 0.002，RE的后β=-0.942，P值= 0.045）。最后，在男性和女性亚组中，难治性患者中的PACER表达高于对照组，非难治性患者中的PACER表达高于对照组。然而，非难治性和难治性患者之间的比较显示仅在女性中有显着结果。评估的lncRNA的表达均与研究参与者的年龄无关。lncRNA的表达水平之间存在强相关性。在UCA1和PACER之间（r  = 0.84，P  <0.0001）以及UCA1和ANRIL之间（（r  = 0.75，P  <0.0001）。两者合计，我们的研究表明癫痫患者外周血中lncRNA的失调，并将其增强为这种神经系统疾病的生物标记。