Zhou Huiting, Song Huihui, Wu Yi, Liu Xiang, Li Jing, Zhao He, Tang Miaomiao, Ji Xiaoyuan, Zhang Lu, Su Yuanyuan, He Yao, Feng Kehong, Jiao Yang, Xu Hua
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China.
Department of Medical Imaging, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu 215137, P.R. China.
Exp Ther Med. 2019 Sep;18(3):2037-2050. doi: 10.3892/etm.2019.7819. Epub 2019 Jul 26.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. At present, the molecular mechanisms underlying ROP are still far from being clearly understood. Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been reported to serve vital regulatory roles in several human diseases. However, it is still unclear how circRNAs are involved in ROP. In the present study, oxygen-induced retinopathy (OIR) murine retinal samples and paired normal tissues were chosen for high-throughput transcriptome RNA sequencing and bioinformatic analyses. As a result, a total of 236 differentially expressed circRNAs, 14 differentially expressed miRNAs, and 9,756 differentially expressed mRNAs were identified in the OIR samples. Gene ontology analysis showed that angiogenesis ranked in the top five upregulated biological processes associated with differential mRNA expression. Then, 66 co-expression pairs of circRNA-mRNA were predicted according to the mRNAs that were enriched in angiogenesis. Furthermore, coregulation prediction was separately performed to identify the differentially expressed miRNAs that targeted angiogenesis-associated circRNAs or mRNAs. Finally, nine differentially expressed circRNAs were predicted to be competing endogenous RNAs by constructing a circRNA-miRNA-mRNA network followed by reverse transcription-quantitative PCR validation. The results of the present study suggest that the identified set of circRNA transcripts and the potential regulatory mechanisms for the development of ROP are worthy of functional studies.
早产儿视网膜病变（ROP）是儿童失明的主要原因。目前，ROP潜在的分子机制仍远未完全清楚。环状RNA（circRNAs）是一类新型的非编码RNA，据报道在几种人类疾病中发挥着重要的调节作用。然而，circRNAs如何参与ROP仍不清楚。在本研究中，选取氧诱导性视网膜病变（OIR）小鼠视网膜样本及配对的正常组织进行高通量转录组RNA测序和生物信息学分析。结果，在OIR样本中总共鉴定出236个差异表达的circRNAs、14个差异表达的miRNAs和9756个差异表达的mRNAs。基因本体分析表明，血管生成在与差异mRNA表达相关的上调生物过程中排名前五。然后，根据在血管生成中富集的mRNAs预测了66对circRNA-mRNA共表达对。此外，分别进行共调控预测以鉴定靶向血管生成相关circRNAs或mRNAs的差异表达miRNAs。最后，通过构建circRNA-miRNA-mRNA网络并进行逆转录定量PCR验证，预测了9个差异表达的circRNAs为竞争性内源RNA。本研究结果表明，所鉴定的circRNA转录本集合以及ROP发生发展的潜在调控机制值得进行功能研究。
