Psychiatric Laboratory and Mental Health Center, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.
Hebei Mental Health Center, Baoding, China.
J Affect Disord. 2019 Feb 15;245:205-212. doi: 10.1016/j.jad.2018.10.363. Epub 2018 Nov 1.
Major depressive disorder (MDD) is a serious psychiatric illness with unclear pathophysiology. As one of the post-transcriptional regulators, prior research has indicated that miRNAs are involved in the pathophysiology of MDD. The aim of this study was to screen the MDD-related miRNAs in the peripheral blood and investigate the target genes of the differentially expressed miRNAs and their potential functions in MDD pathophysiology.
miRNA sequencing was performed using the peripheral blood of patients with MDD and matched controls (cohort A, 10 vs 10). The nominal significant results were validated in an independent sample (cohort B, 72 vs 75) by real-time quantitative polymerase chain reaction (PCR). The target genes of verified miRNAs were predicted using Miranda software. Luciferase assay was used to verify one of the predicted target genes. Furthermore, we analyzed the correlations between the expression of pmiR-chr11 and hippocampal volume.
Ten miRNAs were nominally significantly dysregulated in patients with MDD in cohort A. One of the 10 miRNAs, pmiR-chr11, was significantly dysregulated in cohort B. The pmiR-chr11 could regulate one of the target genes, BRPF1 (bromodomain and PHD finger containing 1), via binding its 3' untranslated region (UTR). The expression of pmiR-chr11 was negatively correlated with hippocampal volume in patients with MDD.
The expression of the miRNAs and mRNAs detected in the peripheral blood may not reflect the expression in the brain.
Our findings suggested that the pmiR-chr11 may influence hippocampal volume by regulating BRPF1 in MDD.
重度抑郁症（MDD）是一种严重的精神疾病，其病理生理学尚不清楚。作为一种转录后调节剂，先前的研究表明 miRNA 参与了 MDD 的病理生理学过程。本研究旨在筛选外周血中的 MDD 相关 miRNA，并研究差异表达 miRNA 的靶基因及其在 MDD 病理生理学中的潜在功能。
使用 MDD 患者和匹配对照者（队列 A，10 例对 10 例）的外周血进行 miRNA 测序。通过实时定量聚合酶链反应（PCR）在独立样本（队列 B，72 例对 75 例）中验证了显著差异的结果。使用 Miranda 软件预测验证 miRNA 的靶基因。通过荧光素酶测定验证了预测靶基因之一。此外，我们分析了 pmiR-chr11 的表达与海马体积之间的相关性。
在队列 A 中，MDD 患者的 10 个 miRNA 表达水平出现显著差异。在队列 B 中，其中一个 miRNA，pmiR-chr11，表达显著失调。pmiR-chr11 可以通过结合其 3'非翻译区（UTR）来调节靶基因 BRPF1（溴结构域和 PHD 指蛋白 1）之一。pmiR-chr11 的表达与 MDD 患者的海马体积呈负相关。
外周血中检测到的 miRNA 和 mRNA 的表达可能不能反映大脑中的表达。
我们的研究结果表明，pmiR-chr11 可能通过调节 BRPF1 影响 MDD 患者的海马体积。
