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环状RNA作为早产新调控因子和生物标志物的鉴定与表征

Identification and Characterization of Circular RNA as a Novel Regulator and Biomarker in Preterm Birth.

作者信息

Ran Yuxin, Yin Nanlin, Huang Dongni, Zhao Yangyu, Yang Jing, Zhang Hanwen, Qi Hongbo

机构信息

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China.

出版信息

Front Bioeng Biotechnol. 2020 Dec 2;8:566984. doi: 10.3389/fbioe.2020.566984. eCollection 2020.

Abstract

Preterm birth (PTB), as the leading cause of neonatal death, is a severe threat to maternal-fetal health. The diagnosis and treatment of PTB are difficult as its underlying mechanism still unknown. Circular RNA (circRNA) is an emerging molecule that plays an essential role in the pathological processes of various diseases. However, it is still unclear whether circRNAs are abnormal or involves in the PTB pathology. In this study, we analyzed RNA-seq data of peripheral blood from preterm and term pregnant women and verified with microarray data. There were 211 circRNA expression disorders in PTB, of which 68 increased and 143 decreased. Bioinformatics analysis revealed that the top 20 circRNAs competitively bind 68 miRNAs, thereby regulating 622 mRNAs mainly related to immunity, inflammation, and nerve activity, which may ultimately contribute to the occurrence of PTB. Moreover, 6 regulatory pairs, including hsa-MORC3_0001-hsa-miR-1248-CHRM2 were the core parts of this mechanism network, which might be therapeutic targets for PTB. Besides, ROC analysis indicated that hsa-ANKFY1_0025, hsa-FAM13B_0019, and hsa-NUSAP1_0010 (AUC = 0.7138, 0.9589, 1.000) have an excellent discrimination ability for PTB. Taken together, we explored for the first time the circRNA expression profile of PTB, and preliminarily analyzed its regulatory mechanism and predictive value for PTB, thus bringing new light to the diagnosis and treatment of PTB.

摘要

早产(PTB)作为新生儿死亡的主要原因,对母婴健康构成严重威胁。由于其潜在机制尚不清楚,PTB的诊断和治疗具有挑战性。环状RNA(circRNA)是一种新兴分子,在各种疾病的病理过程中发挥着重要作用。然而,circRNAs是否异常或参与PTB病理仍不清楚。在本研究中,我们分析了早产和足月孕妇外周血的RNA测序数据,并用微阵列数据进行了验证。PTB中有211种circRNA表达紊乱,其中68种增加,143种减少。生物信息学分析表明,前20种circRNAs竞争性结合68种miRNAs,从而调控622种主要与免疫、炎症和神经活动相关的mRNA,这可能最终导致PTB的发生。此外,包括hsa-MORC3_0001-hsa-miR-1248-CHRM2在内的6个调控对是该机制网络的核心部分,可能是PTB的治疗靶点。此外,ROC分析表明,hsa-ANKFY1_0025、hsa-FAM13B_0019和hsa-NUSAP1_0010(AUC = 0.7138、0.9589、1.000)对PTB具有良好的鉴别能力。综上所述,我们首次探索了PTB的circRNA表达谱,并初步分析了其对PTB的调控机制和预测价值,从而为PTB的诊断和治疗带来了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f72c/7775733/a14a694ec132/fbioe-08-566984-g001.jpg

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