环状RNA在早产儿视网膜病变患儿血浆中的表达变化

张丽亚; 朱攀; 金夏敏; 揭青青; 崔英波; 陈黎丽

doi:10.16766/j.cnki.issn.1674-4152.003909

环状RNA在早产儿视网膜病变患儿血浆中的表达变化

doi: 10.16766/j.cnki.issn.1674-4152.003909

宁波大学附属妇女儿童医院新生儿中心，浙江宁波 315012

基金项目:

浙江省医药卫生科技计划项目 2021KY319

浙江省医药卫生科技计划项目 2021KY324

宁波市科技计划项目 2019A21002

宁波市卫生健康科技计划项目 2023Y21

第四轮宁波市医学重点学科建设计划项目 2022-B17

2022年宁波市第一批医疗卫生高端团队重大攻坚项目 2022020405

详细信息

通讯作者:
陈黎丽，E-mail：chenll202303@163.com

中图分类号: R722.6 R774.1
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- 被引次数: 0
出版历程
- 收稿日期: 2024-03-21
- 网络出版日期: 2025-05-14

Differential expression of circular RNAs in the plasma of premature infants with retinopathy

Newborn Center, Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang 315012, China

摘要

摘要: 目的分析早产儿视网膜病变(ROP)患儿血浆中环状RNA(circRNA)的表达谱变化。方法选取2023年1—8月于宁波大学附属妇女儿童医院住院治疗的ROP患儿3例为ROP组，同期无ROP患儿3例为对照组。采用高通量测序技术检测并筛选出血浆中差异表达的circRNA，应用生物信息学进行基因本体论(GO)注释、京都基因和基因组百科全书(KEGG)分析。利用在线数据库预测circRNA可能靶向的微小RNA(miRNA)。结果与对照组比较，ROP组患者血浆中共有108个circRNA呈显著差异性表达(P＜0.05，差异倍数≥1)，包括41个表达上调和67个表达下调的circRNA。生物信息学分析发现，质子转运ATP合酶、细胞代谢等通路在ROP的发生发展中作用较大。应用miRanda和psRobot软件预测circRNA与miRNA差异表达的关系，绘制circRNA-miRNA调控网络图。结论 ROP组与对照组中circRNA存在差异表达。这些circRNA可能参与ROP的发生、发展过程，有可能成为ROP的新型诊断和治疗的潜在分子标志物。
- 早产儿视网膜病变 /
- 环状RNA /
- 微小RNA /
- 高通量测序 /
- 差异表达谱
Abstract: Objective This study aims to analyze the expression profile changes of circular RNA (circRNA) in the plasma of children with retinopathy of prematurity (ROP). Methods Three children with ROP hospitalized at Women and Children's Hospital of Ningbo University from January 2023 to August 2023 were selected as the ROP group, while three children without ROP during the same period were selected as the control group. High-throughput sequencing technology was used to detect and screen for differentially expressed circRNAs in hemorrhagic plasma, followed by bioinformatic analysis including gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Online databases were employed to predict the potential target microRNAs (miRNAs) of circRNA. Results Compared with the control group, a total of 108 circRNAs were significantly differentially expressed in the plasma of patients in the ROP group (P<0.05, fold change≥1), with 41 upregulated and 67 downregulated circRNAs. Bioinformatics analysis revealed that pathways such as proton-transporting ATP synthase and cellular metabolism play important roles in the occurrence and development of ROP. The relationship between differentially expressed circRNA and miRNA was predicted using miRanda and psRobot software, and a circRNA-miRNA regulatory network diagram was constructed. Conclusion Differential expression of circRNA exists between the ROP group and the control group, suggesting their potential involvement in the occurrence and development of ROP, or as novel molecular markers for diagnosis and treatment of ROP.
- Retinopathy of premature infants /
- Circular RNA /
- MicroRNAs /
- High throughput sequencing /
- Differential expression profile

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图 1 差异表达circRNA MA图

注：横坐标为两样品circRNA表达量之积对2取对数的值，即log₂(A*B)，A和B分别表示circRNA在两样本中的表达量，纵坐标为表达量之商对2取对数的值，即log₂(A/B)。红点表示该组上调circRNA，蓝点表示该组下调circRNA，灰点表示非显著差异表达circRNA。

Figure 1. MA Plot of Differentially Expressed circRNAs

下载: 全尺寸图片幻灯片

图 2 GO富集分析柱状图

横坐标为Go level2等级的term，纵坐标为每个term富集的-lg(P-value)。

Figure 2. GO enrichment analysis for the host genes of circRNA

下载: 全尺寸图片幻灯片

图 3 KEGG Pathway富集结果柱状图

注：横坐标为pathway名称，纵坐标为每个pathway富集的-lg(P-value)。

Figure 3. KEGG Pathway enrichment analysis for the host genes of circRNA

下载: 全尺寸图片幻灯片

表 1 ROP组与正常对照组差异表达的前10位circRNA

Table 1. The top 10 differentially expressed circRNAs between ROP group and normal control group

circRNA	表达情况	log₂倍数变化	差异倍数	P值
hsacirc_023006	高	1.539 898 442	2.907 740 33	0.005 217 30
hsacirc_018939	高	2.822 699 769	7.074 851 02	0.005 511 44
hsacirc_022005	高	1.645 302 529	3.128 134 46	0.005 904 15
hsacirc_032202	高	Inf	Inf	0.005 937 40
hsacirc_039472	高	2.139 503 168	4.406 102 83	0.006 225 46
hsacirc_028841	高	2.443 802 954	5.440 740 25	0.006 307 36
hsacirc_005342	高	3.811 709 842	14.042 324 2	0.006 695 37
hsacirc_014746	高	2.874 289 008	7.332 417 87	0.007 831 36
hsacirc_020683	高	2.690 666 771	6.456 117 21	0.009 795 87
hsacirc_023176	高	1.882 270 457	3.686 547 78	0.010 698 29
hsacirc_000912	低	-Inf	0	0.000 015 10
hsacirc_023530	低	-1.450 429 972	0.365 912 35	0.000 137 53
hsacirc_015864	低	-1.381 069 717	0.383 934 01	0.000 240 20
hsacirc_034631	低	-3.377 044 657	0.096 251 66	0.000 649 55
hsacirc_018196	低	-2.856 604 033	0.138 062 74	0.000 821 47
hsacirc_009338	低	-1.315 048 131	0.401 912 08	0.001 033 38
hsacirc_020848	低	-1.442 505 622	0.367 927 74	0.002 032 14
hsacirc_007605	低	-Inf	0	0.002 250 88
hsacirc_035263	低	-4.510 997 934	0.043 858 55	0.003 878 46
hsacirc_047998	低	-4.307 990 44	0.050 485 38	0.004 055 68
注:Inf 表示无穷大,-Inf 表示无穷小。

下载: 导出CSV

表 2 差异表达的circRNA与miRNA结合位点的预测结果

Table 2. Prediction results of differentially expressed circRNA and miRNA binding sites

表达趋势	circRNAs	数量	前5位miRNAs
上调	hsacirc_023006	64	hsa-miR-23a-3p, hsa-miR-103a-2-5p，hsa-miR-103a-1-5p, hsa-miR-214-3p，hsa-miR-23b-3p
	hsacirc_018939	101	hsa-let-7a-3p, hsa-let-7b-3p, hsa-let-7f-1-3p, hsa-miR-19a-3p, hsa-miR-19b-3p
	hsacirc_022005	1 414	hsa-let-7a-3p, hsa-let-7a-2-3p，hsa-let-7b-3p, hsa-let-7c-3p，hsa-let-7f-1-3p
	hsacirc_032202	75	hsa-miR-29a-3p, hsa-miR-29b-3p，hsa-miR-103a-2-5p, hsa-miR-103a-1-5p, hsa-miR-196a-3p
	hsacirc_039472	227	hsa-miR-22-5p, hsa-miR-106a-3p，hsa-miR-16-2-3p, hsa-miR-34a-5p，hsa-miR-211-3p
下调	hsacirc_000912	2 513	hsa-let-7a-5p, hsa-let-7a-3p，hsa-let-7a-2-3p, hsa-let-7b-5p，hsa-let-7b-3p
	hsacirc_023530	198	hsa-let-7c-3p, hsa-miR-20a-3p，hsa-miR-22-5p, hsa-miR-23a-5p，hsa-miR-23a-3p
	hsacirc_015864	50	hsa-miR-214-3p, hsa-miR-145-3p，hsa-miR-370-5p, hsa-miR-431-3p，hsa-miR-485-3p
	hsacirc_034631	40	hsa-miR-196a-5p, hsa-miR-128-1-5p，hsa-miR-135a-5p, hsa-miR-128-2-5p，hsa-miR-135b-5p
	hsacirc_018196	654	hsa-let-7a-5p, hsa-let-7b-5p，hsa-let-7c-5p, hsa-let-7d-5p，hsa-let-7e-5p

下载: 导出CSV

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