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全转录组测序以揭示与精神分裂症发病机制相关的环状RNA表达模式。

Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis.

作者信息

Long Jianxiong, Shen Bing, Liao Fangping, Cai Hong, Li Jiale, Lu Rumei, Zhong Zhicheng, Gong Zukang, Xu Jianfeng

机构信息

Epidemiology and Biostatistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.

Key Laboratory of Basic Research on Regional Diseases (Guangxi Medical University), School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Eur J Med Res. 2025 Jul 15;30(1):626. doi: 10.1186/s40001-025-02899-4.

DOI:10.1186/s40001-025-02899-4
PMID:40665444
Abstract

BACKGROUND

No objective diagnostic indicators have been identified for schizophrenia (SCZ) because of the complexity of its pathogenesis. Whole-transcriptome analysis may help identify early diagnostic markers. While circular RNAs (circRNAs) have been reported to be involved in the onset and development of many diseases, their association with SCZ remains unclear.

METHODS

This case‒control study analysed 5 pairs of peripheral blood samples from SCZ patients and controls. The samples were subjected to whole transcriptome analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to identify the biological functions and pathways of the circRNAs. The competing endogenous RNA (ceRNA) network was predicted via miRanda, TargetScan, and miRTarBase. Protein-protein interactions were predicted with STRING. In addition, the interaction network between circRNAs and RNA binding proteins (RBPs) was predicted via the catRAPID and starBase databases. The expression of circRNAs was detected via qRT-PCR.

RESULTS

The expression of 38699 circRNAs in the peripheral blood of 5 SCZ patients and 5 paired controls was profiled, and 589 differentially expressed circRNAs (DEcircRNAs) were identified. GO and KEGG analyses revealed that the host genes of these DEcircRNAs' are involved in molecular modifications and pathways such as the TNF and Wnt signalling pathways. A ceRNA network of 252 DEcircRNAs, 297 miRNAs, and 1075 mRNAs was constructed, highlighting potential regulatory molecules in SCZ. Three DEcircRNAs (hsa_circ_0006157, hsa_circ_0071422, and hsa_circ_0071095) were found to be significantly upregulated in patients. In addition, 27 RBPs were identified to bind to these DEcircRNAs, with DDX54 and RBM15B being significantly expressed.

CONCLUSION

Our study provides new insights into circRNAs that could act as potential diagnostic markers for SCZ, namely upregulated hsa_circ_0006157, hsa_circ_0071422, and hsa_circ_0071095. However, further functional validation is warranted to elucidate the precise contributions of these three circRNAs in SCZ.

摘要

背景

由于精神分裂症(SCZ)发病机制复杂,尚未确定客观的诊断指标。全转录组分析可能有助于识别早期诊断标志物。虽然环状RNA(circRNA)已被报道参与多种疾病的发生和发展,但其与SCZ的关联仍不清楚。

方法

本病例对照研究分析了5对SCZ患者和对照的外周血样本。对样本进行全转录组分析。随后进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,以确定circRNA的生物学功能和途径。通过miRanda、TargetScan和miRTarBase预测竞争性内源RNA(ceRNA)网络。用STRING预测蛋白质-蛋白质相互作用。此外,通过catRAPID和starBase数据库预测circRNA与RNA结合蛋白(RBP)之间的相互作用网络。通过qRT-PCR检测circRNA的表达。

结果

分析了5例SCZ患者和5对配对对照外周血中38699种circRNA的表达谱,鉴定出589种差异表达的circRNA(DEcircRNA)。GO和KEGG分析表明,这些DEcircRNA的宿主基因参与分子修饰以及TNF和Wnt信号通路等途径。构建了一个由252种DEcircRNA、297种miRNA和1075种mRNA组成的ceRNA网络,突出了SCZ中潜在的调控分子。发现3种DEcircRNA(hsa_circ_0006157、hsa_circ_0071422和hsa_circ_0071095)在患者中显著上调。此外,鉴定出27种RBP与这些DEcircRNA结合,其中DDX54和RBM15B表达显著。

结论

我们的研究为circRNA提供了新的见解,其可能作为SCZ的潜在诊断标志物,即上调的hsa_circ_0006157、hsa_circ_0071422和hsa_circ_0071095。然而,需要进一步的功能验证来阐明这三种circRNA在SCZ中的精确作用。

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