Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2021 Nov;71(11):2249-2259. doi: 10.1007/s12031-020-01772-9. Epub 2021 Jan 5.
Long non-coding RNAs (lncRNAs) play a decisive role in the development of the central nervous system and modulation, differentiation, and function of neurons. Thus, any abnormal pattern of expression of these transcripts might alter normal development leading to neuropsychiatric disorders. In this regard, transcripts of brain-derived neurotrophic factor (BDNF) and four BDNF-associated lncRNAs (BDNF-AS, MIR137HG, MIAT, and PNKY) were evaluated in the peripheral blood of schizophrenia (SCZ) patients as well as normal subjects. The results indicated that the relative expression (RE) of PNKY was higher in SCZ patients as compared with controls (posterior beta of RE = 2.605, P value = 0.006) and in female patients compared with female controls (posterior beta of RE = 2.831, P value < 0.0001). BDNF expression was also higher in SCZ patients when compared with controls (posterior beta of RE = 0.64, P value < 0.036). Finally, a correlation was detected between the disease status and gender in terms of BDNF-AS expression (P value = 0.026). An inverse correlation was also found between levels of PNKY and age in the control group (r = - 0.30, P value < 0.0001). Expressions of BDNF and all lncRNAs were correlated with each other in both patients and controls. PNKY had the best diagnostic power among all assessed genes in the identification of disease status (area under curve = 0.78). BDNF, BDNF-AS, MIR137HG, and MIAT genes could discriminate SCZ patients from normal subjects with diagnostic power of 71%, 72%, 67%, and 68%, respectively. The current investigation suggests the possibility of the application of transcript levels of lncRNAs as an SCZ diagnostic marker. However, it warrants further studies in larger sample sizes.
长链非编码 RNA（lncRNA）在中枢神经系统的发育以及神经元的调节、分化和功能中起着决定性的作用。因此，这些转录本的任何异常表达模式都可能改变正常发育，导致神经精神疾病。在这方面，评估了精神分裂症（SCZ）患者和正常对照者外周血中脑源性神经营养因子（BDNF）和四个 BDNF 相关的长链非编码 RNA（BDNF-AS、MIR137HG、MIAT 和 PNKY）的转录本。结果表明，与对照组相比，SCZ 患者的 PNKY 相对表达（RE）更高（RE 的后β=2.605，P 值=0.006），与女性对照组相比，女性患者的 PNKY 相对表达（RE）更高（RE 的后β=2.831，P 值<0.0001）。与对照组相比，SCZ 患者的 BDNF 表达也更高（RE 的后β=0.64，P 值<0.036）。最后，BDNF-AS 的表达在疾病状态和性别之间存在相关性（P 值=0.026）。在对照组中，还发现 PNKY 的水平与年龄呈负相关（r=-0.30，P 值<0.0001）。在患者和对照组中，BDNF 和所有 lncRNA 的表达彼此相关。在所有评估的基因中，PNKY 在识别疾病状态方面具有最佳的诊断能力（曲线下面积=0.78）。BDNF、BDNF-AS、MIR137HG 和 MIAT 基因分别可以将 SCZ 患者与正常受试者区分开来，其诊断能力分别为 71%、72%、67%和 68%。目前的研究表明，lncRNA 转录本水平作为 SCZ 诊断标志物的可能性。然而，这需要在更大的样本量中进行进一步的研究。
