Preliminary analysis of differentially expressed circRNA of patients with Alzheimer's disease

doi:10.3969/j.issn.1673-8640.2021.11.005

Abstract

Abstract:

Objective To investigate expression profiles of circular RNA（circRNA） in peripheral blood of patients with Alzheimer's disease（AD）,and to predict its downstream microRNA（miRNA） targets and the biological function of host gene. Methods Expression profiles of circRNA in peripheral blood from 3 AD patients（AD group） and 3 healthy subjects（healthy control group） were analyzed by microarray assay. Differentially expressed circRNA between the 2 groups were identified,and bioinformatics prediction was performed. Two differentially expressed circRNA were further confirmed by real-time fluorescence quantitative polymerase chain reaction（RT-qPCR） in a validation cohort of 30 AD patients and 22 healthy subjects. Results A total of 144 circRNA（fold change>1.5,P<0.05） were identified to be differentially expressed in AD patients as compared to healthy subjects,which included 72 circRNA upregulated and 72 circRNA downregulated. Gene Ontology（GO）was performed to investigate biological functions of their host genes. Host genes may participate in various biological processes,such as reproductive process,regulation of mitogen-activated protein kinase cascade,regulation of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis showed that some vital pathways could also be influenced by the differentially expressed circRNA,including inflammatory bowel disease,vascular endothelial growth factor（VEGF）,endocytosis,gamma receptor for the Fc region of immunoglobulin G（FcγR） mediated phagocytosis. Two differentially expressed circRNA were chosen for further validation,including one upregulated circRNA（hsa_circ_0018905） and one downregulated circRNA（hsa_circ_0024825）. The RT-qPCR results showed that compared to healthy control group the relative expression of hsa_circ_0018905 was upregulated in AD group（P<0.05）,and hsa_circ_0024825 was downregulated between AD group and healthy control group（P<0.01）,which were consistent with the microarray assay results. Conclusions This study identifys a few differentially expressed circRNA between AD patients and healthy subjects,which may exhibit a regulatory role in the occurrence and development of AD by the function as "miRNA sponge".

Key words: Circular RNA, MicroRNA, Alzheimer's disease

CLC Number:

R393

LOU Xiaoyan, WANG Tao, GAO Qiong, LU Wei, LI Dan, LI Zhenhua, LIN Ping. Preliminary analysis of differentially expressed circRNA of patients with Alzheimer's disease[J]. Laboratory Medicine, 2021, 36(11): 1114-1120.

Figures/Tables 5

References 15

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circRNA名称	差异倍数	P值	亲本基因	染色体定位	表达变化
hsa_circ_0018905	63.47	0.002	SAMD8	chr10	上调
hsa_circ_0007352	40.86	0.005	AKAP17A	chrX	上调
hsa_circ_0006148	7.27	0.048	SAMD8	chr10	上调
hsa_circ_0002292	3.01	0.002	NADK2	chr5	上调
hsa_circ_0002474	2.36	0.042	PDE5A	chr4	上调
hsa_circ_0067209	2.27	0.018	EEFSEC	chr3	上调
hsa_circ_0070805	1.79	0.019	PDE5A	chr4	上调
hsa_circ_0000681	1.67	0.003	PRKCB	chr16	上调
hsa_circ_0052941	1.63	0.009	ATAD2B	chr2	上调
hsa_circ_0071036	1.59	0.021	INPP4B	chr4	上调
hsa_circ_0015980	4.50	0.004	PPP1R12B	chr1	下调
hsa_circ_0024825	4.29	0.005	ST3GAL4	chr11	下调
hsa_circ_0087004	3.63	0.003	CLTA	chr9	下调
hsa_circ_0035197	3.28	0.001	ATP8B4	chr15	下调
hsa_circ_0001707	3.28	0.002	ABCA13	chr7	下调
hsa_circ_0029410	2.72	0.004	GLT1D1	chr12	下调
hsa_circ_0004662	2.45	0.023	SOD2	chr6	下调
hsa_circ_0029405	1.82	0.017	GLT1D1	chr12	下调
hsa_circ_0006435	1.78	0.019	UGCG	chr9	下调
hsa_circ_0038799	1.69	0.010	XPO6	chr16	下调

circRNA名称	差异倍数	P值	亲本基因	染色体定位	表达变化
hsa_circ_0018905	63.47	0.002	SAMD8	chr10	上调
hsa_circ_0007352	40.86	0.005	AKAP17A	chrX	上调
hsa_circ_0006148	7.27	0.048	SAMD8	chr10	上调
hsa_circ_0002292	3.01	0.002	NADK2	chr5	上调
hsa_circ_0002474	2.36	0.042	PDE5A	chr4	上调
hsa_circ_0067209	2.27	0.018	EEFSEC	chr3	上调
hsa_circ_0070805	1.79	0.019	PDE5A	chr4	上调
hsa_circ_0000681	1.67	0.003	PRKCB	chr16	上调
hsa_circ_0052941	1.63	0.009	ATAD2B	chr2	上调
hsa_circ_0071036	1.59	0.021	INPP4B	chr4	上调
hsa_circ_0015980	4.50	0.004	PPP1R12B	chr1	下调
hsa_circ_0024825	4.29	0.005	ST3GAL4	chr11	下调
hsa_circ_0087004	3.63	0.003	CLTA	chr9	下调
hsa_circ_0035197	3.28	0.001	ATP8B4	chr15	下调
hsa_circ_0001707	3.28	0.002	ABCA13	chr7	下调
hsa_circ_0029410	2.72	0.004	GLT1D1	chr12	下调
hsa_circ_0004662	2.45	0.023	SOD2	chr6	下调
hsa_circ_0029405	1.82	0.017	GLT1D1	chr12	下调
hsa_circ_0006435	1.78	0.019	UGCG	chr9	下调
hsa_circ_0038799	1.69	0.010	XPO6	chr16	下调

circRNA名称	MRE1	MRE2	MRE3
上调
hsa_circ_0018905	hsa-miR-505-5p	hsa-miR-16-1-3p	hsa-miR-636
hsa_circ_0007352	hsa-miR-2682-3p	hsa-miR-6836-5p	hsa-miR-6132
hsa_circ_0006148	hsa-miR-141-5p	hsa-miR-98-3p	hsa-let-7f-1-3p
hsa_circ_0002292	hsa-miR-8087	hsa-miR-3972	hsa-miR-335-3p
hsa_circ_0002474	hsa-miR-670-3p	hsa-miR-583	hsa-miR-455-3p
hsa_circ_0067209	hsa-miR-8082	hsa-miR-146b-3p	hsa-miR-6876-3p
hsa_circ_0070805	hsa-miR-29b-1-5p	hsa-miR-670-3p	hsa-miR-29a-5p
hsa_circ_0000681	hsa-miR-181c-5p	hsa-miR-181d-5p	hsa-miR-181a-5p
hsa_circ_0052941	hsa-miR-372-3p	hsa-miR-93-5p	hsa-miR-106a-5p
hsa_circ_0071036	hsa-miR-376a-3p	hsa-miR-489-3p	hsa-miR-29b-3p
下调
hsa_circ_0015980	hsa-miR-149-5p	hsa-miR-8057	hsa-miR-449b-3p
hsa_circ_0024825	hsa-miR-708-5p	hsa-miR-1229-5p	hsa-miR-4640-5p
hsa_circ_0087004	hsa-miR-5193	hsa-miR-877-3p	hsa-miR-6760-5p
hsa_circ_0035197	hsa-miR-605-3p	hsa-miR-101-5p	hsa-miR-31-5p
hsa_circ_0001707	hsa-miR-22-5p	hsa-miR-22-3p	hsa-miR-599
hsa_circ_0029410	hsa-miR-197-3p	hsa-miR-412-3p	hsa-miR-146b-3p
hsa_circ_0004662	hsa-miR-4520-2-3p	hsa-miR-208b-5p	hsa-miR-4713-5p
hsa_circ_0029405	hsa-miR-764	hsa-miR-19a-3p	hsa-miR-9-5p
hsa_circ_0006435	hsa-miR-335-3p	hsa-miR-4464	hsa-miR-942-5p
hsa_circ_0038799	hsa-miR-429	hsa-miR-200b-3p	hsa-miR-200c-3p

circRNA名称	MRE1	MRE2	MRE3
上调
hsa_circ_0018905	hsa-miR-505-5p	hsa-miR-16-1-3p	hsa-miR-636
hsa_circ_0007352	hsa-miR-2682-3p	hsa-miR-6836-5p	hsa-miR-6132
hsa_circ_0006148	hsa-miR-141-5p	hsa-miR-98-3p	hsa-let-7f-1-3p
hsa_circ_0002292	hsa-miR-8087	hsa-miR-3972	hsa-miR-335-3p
hsa_circ_0002474	hsa-miR-670-3p	hsa-miR-583	hsa-miR-455-3p
hsa_circ_0067209	hsa-miR-8082	hsa-miR-146b-3p	hsa-miR-6876-3p
hsa_circ_0070805	hsa-miR-29b-1-5p	hsa-miR-670-3p	hsa-miR-29a-5p
hsa_circ_0000681	hsa-miR-181c-5p	hsa-miR-181d-5p	hsa-miR-181a-5p
hsa_circ_0052941	hsa-miR-372-3p	hsa-miR-93-5p	hsa-miR-106a-5p
hsa_circ_0071036	hsa-miR-376a-3p	hsa-miR-489-3p	hsa-miR-29b-3p
下调
hsa_circ_0015980	hsa-miR-149-5p	hsa-miR-8057	hsa-miR-449b-3p
hsa_circ_0024825	hsa-miR-708-5p	hsa-miR-1229-5p	hsa-miR-4640-5p
hsa_circ_0087004	hsa-miR-5193	hsa-miR-877-3p	hsa-miR-6760-5p
hsa_circ_0035197	hsa-miR-605-3p	hsa-miR-101-5p	hsa-miR-31-5p
hsa_circ_0001707	hsa-miR-22-5p	hsa-miR-22-3p	hsa-miR-599
hsa_circ_0029410	hsa-miR-197-3p	hsa-miR-412-3p	hsa-miR-146b-3p
hsa_circ_0004662	hsa-miR-4520-2-3p	hsa-miR-208b-5p	hsa-miR-4713-5p
hsa_circ_0029405	hsa-miR-764	hsa-miR-19a-3p	hsa-miR-9-5p
hsa_circ_0006435	hsa-miR-335-3p	hsa-miR-4464	hsa-miR-942-5p
hsa_circ_0038799	hsa-miR-429	hsa-miR-200b-3p	hsa-miR-200c-3p