Gou Mengzhuang, Pan Shujuan, Tong Jinghui, Zhou Yanfang, Han Jiarui, Xie Ting, Yu Ting, Feng Wei, Li Yanli, Chen Song, Cui Yimin, Tian Baopeng, Tan M D Shuping, Wang Zhiren, Luo Xingguang, Li Chiang-Shan R, Zhang Ping, Huang Junchao, Hong L Elliot, Tan Yunlong, Tian Li
Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
Department of Pharmacy, Peking University First Hospital, Beijing, China.
J Psychiatr Res. 2021 Apr;136:358-365. doi: 10.1016/j.jpsychires.2021.02.003. Epub 2021 Feb 14.
MicroRNA (miR)-181b-5p is considered to be involved in the pathogenesis of schizophrenia, and one of its regulatory target genes BCL-2 (B-cell lymphoma 2) is suggested to associate with cognition of schizophrenia. Cognitive deficit is a core trait of schizophrenia. However, it remains unclear whether miR-181b-5p affects cognition and its possible pathway in schizophrenia. We hypothesized that miR-181b-5p affects cognition by targeting BCL-2 mRNA and downregulating BCL-2 protein expression in schizophrenia patients. In this study, first-episode patients with schizophrenia (FEPS, n = 123) and age- and gender-matched healthy controls (HCs, n = 50) were enrolled in Chinese populations. Expression levels of miR-181b-5p and BCL-2 mRNA in peripheral whole blood were measured with quantitative real-time PCR (Q-PCR) and BCL-2 protein in plasma were measured with Enzyme Linked Immunosorbent Assay (ELISA). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Peripheral blood miR-181b-5p expression level was significantly upregulated (p = 0.001) whereas BCL-2 mRNA and BCL-2 protein levels were significantly downregulated (p = 0.002, p = 0.023 respectively) in the FEPS compared with those in the HCs. The miR-181b-5p level was negatively (p = 0.005), whereas the BCL-2 mRNA level was positively (p < 0.001), correlated with working memory in FEPS. Mediating effect analysis showed that the effect of miR-181b-5p on working memory in the FEPS was exerted via targeting BCL-2 mRNA. MiR-181b-5p in combination with BCL-2 mRNA might be suggested as potential biomarker for schizophrenia in our discovery sample. In conclusion, overexpressed miR-181b-5p may affect cognitive function in patients with schizophrenia.
微小RNA（miR）-181b-5p被认为参与了精神分裂症的发病机制，其调控靶基因之一BCL-2（B细胞淋巴瘤2）被认为与精神分裂症的认知有关。认知缺陷是精神分裂症的核心特征。然而，miR-181b-5p是否影响精神分裂症的认知及其可能的途径仍不清楚。我们假设miR-181b-5p通过靶向精神分裂症患者的BCL-2 mRNA并下调BCL-2蛋白表达来影响认知。在本研究中，纳入了中国人群中的首发精神分裂症患者（FEPS，n = 123）以及年龄和性别匹配的健康对照（HCs，n = 50）。采用定量实时PCR（Q-PCR）检测外周全血中miR-181b-5p和BCL-2 mRNA的表达水平，采用酶联免疫吸附测定（ELISA）检测血浆中BCL-2蛋白的水平。用阳性和阴性症状量表（PANSS）评估精神病理学，使用MATRICS共识认知成套测验（MCCB）评估认知功能。与HCs相比，FEPS外周血miR-181b-5p表达水平显著上调（p = 0.001），而BCL-2 mRNA和BCL-2蛋白水平显著下调（分别为p = 0.002，p = 0.023）。在FEPS中，miR-181b-5p水平与工作记忆呈负相关（p = 0.005），而BCL-2 mRNA水平与工作记忆呈正相关（p < 0.001）。中介效应分析表明，miR-181b-5p对FEPS工作记忆的影响是通过靶向BCL-2 mRNA实现的。在我们的发现样本中，miR-181b-5p与BCL-2 mRNA的组合可能被认为是精神分裂症的潜在生物标志物。总之，miR-181b-5p过表达可能影响精神分裂症患者的认知功能。
