环状 RNA 在人胎盘绒毛和蜕膜中的表达谱及复发性自然流产药物的预测。

Expression profiles of circular RNA in human placental villus and decidua and prediction of drugs for recurrent spontaneous abortion.

机构信息

NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Pharmacy, Fudan University, Shanghai, China.

The Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Am J Reprod Immunol. 2022 Jul;88(1):e13578. doi: 10.1111/aji.13578. Epub 2022 May 29.

DOI:10.1111/aji.13578

PMID:35583158

Abstract

PROBLEM

We aimed to evaluate potential biomarkers and candidate drugs for recurrent spontaneous abortion (RSA) and explore functional circular RNA pathways involved in regulating RSA.

METHOD OF STUDY

Expression profiles of placental villus and decidua samples derived from females with RSA and those with healthy pregnancies who underwent induced abortion were analyzed using high-throughput RNA whole transcriptome sequencing. Abnormally expressed circular RNAs in a larger cohort of samples were validated using real-time quantitative polymerase chain reaction. Drug discovery and molecular docking were performed using online databases and the Autodock tool, respectively.

RESULTS

In total, 2103 and 2160 circular RNAs were detected in three pairs of villi and three pairs of decidual tissues, respectively. A total of 22 circular RNAs, 58 miRNAs, and 393 mRNAs with significantly different expression patterns were identified. Five circular RNAs were verified, and the expression of hsa_circ_0088485 was significantly upregulated in the RSA group (P = .041) with a high area under the curve value (.727), sensitivity (76.5%), and specificity (64.7%). GO and KEGG enrichment analyses indicated that differentially expressed genes were associated with angiogenesis and cell adhesion. Drug discovery and molecular docking were analyzed based on 93 differentially expressed mRNAs of the ceRNA network. A total of 36 chemicals were identified as putative bioactive molecules for RSA, and one representative chemical was identified for docking with six proteins.

CONCLUSIONS

These findings provide novel insights into the mechanism of regulation of RSA by circular RNA and its clinical diagnosis and treatment.

摘要

问题

我们旨在评估复发性自然流产（RSA）的潜在生物标志物和候选药物，并探讨参与调节 RSA 的功能性环状 RNA 通路。

研究方法

使用高通量 RNA 全转录组测序分析源自 RSA 女性和因流产而行刮宫术的健康妊娠女性的胎盘绒毛和蜕膜样本的表达谱。使用实时定量聚合酶链反应验证更大样本队列中异常表达的环状 RNA。使用在线数据库和 Autodock 工具分别进行药物发现和分子对接。

结果

总共在三对绒毛和三对蜕膜组织中检测到 2103 和 2160 个环状 RNA。总共鉴定出 22 个环状 RNA、58 个 miRNA 和 393 个表达模式差异显著的 mRNAs。验证了 5 个环状 RNA，hsa_circ_0088485 在 RSA 组中的表达显著上调（P =.041），曲线下面积（AUC）值高（.727），灵敏度为 76.5%，特异性为 64.7%。GO 和 KEGG 富集分析表明差异表达基因与血管生成和细胞黏附有关。基于 ceRNA 网络的 93 个差异表达 mRNA 进行药物发现和分子对接分析。共鉴定出 36 种化学物质为 RSA 的潜在生物活性分子，并用 6 种蛋白质进行了代表性化学物质的对接。