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Dysregulation of NF-κB-Associated lncRNAs in Multiple Sclerosis Patients.
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-06-29 , DOI: 10.1007/s12031-020-01628-2
Amin Safa 1, 2 , Shahram Arsang-Jang 3 , Mohammad Taheri 4 , Mir Davood Omrani 5 , Soudeh Ghafouri-Fard 4
Affiliation  

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of several complex disorders such as immune-related disorders. Multiple sclerosis (MS) as an inflammatory disorder of the central nervous system has been associated with aberrant expression of several lncRNAs. In the current study, we assessed expression of NF-κB-, autophagy-, and obesity-associated lncRNAs/genes and two inflammatory cytokines in the peripheral blood of MS patients and healthy controls. LNC-MKI67IP was down-regulated in total MS patients compared with total controls (P value < 0.0001). However, when comparing its expression in a gender-based manner, no significant difference was found between patients and controls. Expression of HNF1A-AS1 was significantly lower in total MS patients and patients of both sexes when compared with the matched controls (P value < 0.0001; P value = 0.03; P value = 0.004, respectively). Expression of LINC00305 had a similar pattern to HNF1A-AS1 (P value < 0.0001; P value = 0.005; P value < 0.0001, respectively). Expressions of other assessed NF-κB associated lncRNAs were not different between cases and controls. Expression of IL-1B was significantly lower in total MS patients compared with total controls (P value < 0.0001). Such decreased expression was detected in female patients compared with female controls as well (P value < 0.0001). Expression of IL-6 was not different between cases and controls. Expression of CEBPA was higher in total MS patients compared with controls (P value = 0.047). However, when dividing study participants into male and female subgroups, no significant difference was detected between cases and gender-matched controls. There were no significant difference in the expression of any assessed autophagy-associated lncRNAs between cases and controls. ATG5, CEBPA, HNF1A-AS1, IL-1B, LINC00305, and LNC-MKI67IP could differentiate disease status with diagnostic power values of 0.781, 0.582, 0.744, 0.76, 0.926, and 0.703, respectively. Expression levels of ADINR and CHAST were correlated with age of MS patients and disease duration, respectively (r = 0.33, P < 0.0001; r = 0.34, P < 0.0001, respectively). The present study highlighted the role of a number lncRNAs in the pathogenesis of MS and supported the previous data regarding aberrant expression of these transcripts in this immune-related disorder.



中文翻译:

多发性硬化症患者中 NF-κB 相关 lncRNA 的失调。

据报道,长链非编码 RNA (lncRNA) 参与了几种复杂疾病的发病机制,例如免疫相关疾病。多发性硬化症 (MS) 作为中枢神经系统的一种炎症性疾病,与几种 lncRNA 的异常表达有关。在目前的研究中,我们评估了 MS 患者和健康对照外周血中 NF-κB、自噬和肥胖相关的 lncRNA/基因和两种炎性细胞因子的表达。与总对照相比,LNC-MKI67IP在总 MS 患者中下调(P值 < 0.0001)。然而,当以基于性别的方式比较其表达时,患者和对照之间没有发现显着差异。HNF1A-AS1的表达与匹配的对照相比,MS 患者总数和男女患者中的显着降低(分别为P值 < 0.0001;P值 = 0.03;P值 = 0.004)。LINC00305 的表达与HNF1A-AS1具有相似的模式(分别为P值 < 0.0001;P值 = 0.005;P值 < 0.0001)。其他评估的 NF-κB 相关 lncRNA 的表达在病例和对照之间没有差异。IL-1B在 MS 患者中的表达显着低于对照组(P值 < 0.0001)。与女性对照相比,在女性患者中也检测到这种降低的表达(P值 < 0.0001)。IL-6 的表达在病例和对照之间没有差异。与对照组相比,总 MS 患者中CEBPA 的表达更高(P值 = 0.047)。然而,当将研究参与者分为男性和女性亚组时,病例和性别匹配的对照组之间没有检测到显着差异。病例和对照之间任何评估的自噬相关 lncRNA 的表达没有显着差异。ATG5 , CEBPA , HNF1A-AS1 , IL-1B , LINC00305LNC-MKI67IP可以区分疾病状态,诊断功效值分别为0.781、0.582、0.744、0.76、0.9260.703ADINRCHAST 的表达水平分别与 MS 患者的年龄和病程相关(分别为r  = 0.33,P  < 0.0001;r  = 0.34,P  < 0.0001)。本研究强调了许多 lncRNA 在 MS 发病机制中的作用,并支持了先前关于这些转录本在这种免疫相关疾病中异常表达的数据。

更新日期:2020-07-01
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