Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder.
Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder.
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DOI：
10.1038/s41398-021-01746-4
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发表时间：
2021-12-10
影响因子：
6.8
通讯作者：
Turecki G
中科院分区：
文献类型：
--
作者：
Lin R;Lopez JP;Cruceanu C;Pierotti C;Fiori LM;Squassina A;Chillotti C;Dieterich C;Mellios N;Turecki G
大脑中的基因表达失调与双相情感障碍有关，但对非编码RNA的作用知之甚少。环状RNA是一类新的长链非编码RNA，最近被证明在大脑发育和功能中具有重要作用。然而，它们在精神疾病（包括双相情感障碍）中的潜在作用尚未得到很好的研究。在这项研究中，我们分析了双相情感障碍患者脑组织中的环状RNA。首先在来自由患有双相情感障碍（N = 13）和神经典型对照（N = 13）的个体组成的群组的前扣带皮层的样品中进行总RNA测序，并且使用“circtools”鉴定和分析环状RNA。通过RT-qPCR验证显著环状RNA，并在独立队列（24例双相情感障碍病例和27例对照）的前扣带皮层中复制。此外，我们使用从双相患者（N = 19）和健康对照（N = 12）收集的B淋巴母细胞进行了体外研究，以研究锂治疗后环状RNA的反应。在发现RNA测序分析中，26个环状RNA在双相情感障碍病例和对照组之间显著差异表达（FDR < 0.1）。其中，circCCNT 2经RT-qPCR验证，显示在双相情感障碍中显著上调（p = 0.03）。在一个独立的死后人类前扣带皮层队列和B淋巴母细胞培养中，双相情感障碍的这种上调被复制。此外，circCCNT 2表达在体外响应锂处理而降低。总之，我们的研究是第一个将circCCNT 2与双相情感障碍和锂治疗相关联的研究。
Gene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using “circtools”. Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
4.6
作者：
Barrett, Steven P.;Salzman, Julia
通讯作者：
Salzman, Julia
影响因子：
17.7
作者：
Cruceanu, Cristiana;Tan, Powell Patrick Cheng;Turecki, Gustavo
通讯作者：
Turecki, Gustavo
影响因子：
4.1
作者：
Dudekulay, Dawood B.;Panda, Amaresh C.;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
64.5
作者：
ARNBERG, AC;VANOMMEN, GJB;BORST, P
通讯作者：
BORST, P