Liansheng Zhao1, Xiao Yang1, Lijun Cui2, Jinxue Wei1, Peiyan Ni1, Mingli Li1, Yingcheng Wang1, Yin He1, Xiaojing Li1, Sugai Liang1, Yang Tian1, Qiang Wang1, Wei Cui2, Dongtao Lin3, Xiaohong Ma4, Tao Li1. 1. 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. 2. Hebei Mental Health Center, Baoding, China. 3. College of Foreign Languages and Cultures, Sichuan University, Chengdu, China. 4. 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. Electronic address: maxiaohong@scu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: The expression of the miRNAs and mRNAs detected in the peripheral blood may not reflect the expression in the brain. CONCLUSIONS: Our findings suggested that the pmiR-chr11 may influence hippocampal volume by regulating BRPF1 in MDD.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: The expression of the miRNAs and mRNAs detected in the peripheral blood may not reflect the expression in the brain. CONCLUSIONS: Our findings suggested that the pmiR-chr11 may influence hippocampal volume by regulating BRPF1 in MDD.