Effect of amylin on expression profiles of circRNAs and mRNAs in brain tissue of Alzheimer's disease mice
- Journal of Army Medical University Vol. 45, Issue 19, Pages: 2018-2028(2023)
- 作者机构：
1.233004 安徽 蚌埠，蚌埠医学院第一附属医院神经内科
2.400042 重庆，陆军特色医学中心神经内科
- 作者简介：
- 基金信息：the General Program of National Natural Science Foundation of China(81771177)
DOI：10.16016/j.2097-0927.202304089
CLC： R745.7;R966;R977.6Received：21 April 2023，
Revised：2023-05-17，
Published：15 October 2023
- 稿件说明：
移动端阅览
Mingliang HOU, Linqiu MA, Jinping LI, et al. Effect of amylin on expression profiles of circRNAs and mRNAs in brain tissue of Alzheimer's disease mice[J]. Journal of Army Medical University, 2023, 45(19): 2018-2028.
Mingliang HOU, Linqiu MA, Jinping LI, et al. Effect of amylin on expression profiles of circRNAs and mRNAs in brain tissue of Alzheimer's disease mice[J]. Journal of Army Medical University, 2023, 45(19): 2018-2028. DOI： 10.16016/j.2097-0927.202304089.
摘要
目的
2
研究胰淀素(islet amyloid polypeptide
IAPP)腹腔注射对阿尔茨海默病(Alzheimer’s disease
AD)小鼠和野生型(wild-type，WT)小鼠脑组织中环状RNA(circular RNA
circRNA)和信使RNA(messenger RNA
mRNA)表达谱的影响。
方法
2
选取10月龄20~30 g雄性APP/PS1转基因AD模型小鼠和C57 WT小鼠各6只，把6只AD小鼠和WT小鼠使用随机数字表法分成2组，每组3只。腹腔注射IAPP的AD小鼠(AD
+IAPP
)作为实验组，腹腔注射IAPP的WT小鼠(WT
+IAPP
)作为对照组，腹腔注射相同剂量的磷酸盐缓冲液(PBS)的AD小鼠(AD
+PBS
)和WT小鼠(WT
+PBS
)作为空白对照组。干预结束后，提取4组小鼠脑组织总RNA，进行基因芯片测序，筛选出AD
+IAPP
与WT
+IAPP
相比差异表达的circRNA和mRNA，以及AD
+PBS
与WT
+PBS
相比差异表达的circRNA和mRNA。在AD
+IAPP
与WT
+IAPP
相比筛选出来的差异circRNA中，选取6个差异表达的circRNA，进行实时定量聚合酶链反应(qRT-PCR)验证基因芯片结果的可靠性。对差异表达的mRNA进行基因本体论(gene ontology
GO)富集分析与京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes
KEGG)通路富集分析。随后构建显著差异表达的circRNA_45921的ceRNA(competitive endogenous RNA)网络。
结果
2
AD
+IAPP
与WT
+IAPP
比较，显著差异表达的circRNA共有237个，其中157个上调，80个下调；显著差异表达mRNA共有663个，其中348个上调，315个下调。qRT-PCR结果显示6个差异表达的circRNA与基因芯片结果一致，基因芯片测序结果可靠。GO富集分析显示差异表达上调的mRNA在核苷磷酸结合、细胞器、含磷酸盐化合物代谢过程等GO条目显著富集；差异表达下调的mRNA在跨膜信号受体活性、超分子纤维、组织发育等GO条目显著富集。KEGG富集分析显示差异表达上调的mRNA主要富集于胰岛素分泌、氧化磷酸化、帕金森病等信号通路；差异表达下调的mRNA主要富集于神经活性配体-受体相互作用、钙信号通路、酪氨酸代谢、苯丙氨酸代谢等信号通路。CeRNA网络显示circRNA_45921/miR-34c-5p/Eef2k调控网络可能在IAPP功能发挥中具有作用。
结论
2
腹腔注射IAPP改变AD小鼠和WT小鼠脑组织中circRNA和mRNA的表达谱。差异表达的Paip2、Cdon、Ttr和circRNA_45921/miR-34c-5p/Eef2k调控网络可能在IAPP调节AD的发生发展中起作用。
Abstract
Objective
2
To investigate the effects of intraperitoneal injection of islet amyloid polypeptide (IAPP) on the expression profiles of circular RNAs (circRNAs) and messenger RNAs (mRNAs) in the brain tissue of Alzheimer's disease (AD) mice and wild-type (WT) mice.
Methods
2
Six 10-month-old male APP/PS1 transgenic AD model and C57 WT mice (20~30 g) were employed in this study. They were randomly divided into 2 groups
and further assigned into AD+IAPP (AD mice with IAPP intraperitoneal injection)
WT+IAPP (WT mice with IAPP intraperitoneal injection)
AD+PBS (AD mice injected with same dose of PBS intraperitoneally) and WT+PBS (WT mice with intraperitoneal injection of PBS) groups (
n
=3). After the intervention
total RNA was extracted from the brain tissue of 4 groups of mice
and gene chip sequencing was performed to screen differentially expressed circRNAs and mRNAs between AD+IAPP and WT+IAPP mice and between AD+PBS and WT+PBS mice. Among the differentially expressed circRNAs between AD+IAPP and WT+IAPP mice
6 circRNAs were selected and subjected to real-time quantitative polymerase chain reaction (qRT-PCR) to verify the reliability of the microarray results. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis were performed on the differentially expressed mRNAs. Subsequently
a competitive endogenous RNA (ceRNA) network was constructed for significantly differentially expressed circRNA_45921.
Results
2
There were 237 circRNAs significantly differentially expressed between AD+IAPP and WT+IAPP mice
of which 157 were up-regulated and 80 were down-regulated. Totally 663 significantly differentially expressed mRNAs were found
including 348 up-regulated and 315 down-regulated. The results of qRT-PCR showed that the differential expression of 6 circRNAs was consistent with the results of gene chip
indicating that the results of gene chip sequencing were reliable. GO enrichment analysis revealed that differentially up-regulated mRNAs were significantly enriched in nucleoside phosphate binding
organelles and metabolism processes of phosphate containing compounds. The differentially down-regulated mRNAs were significantly enriched in transmembrane signal receptor activity
supramolecular fibers and tissue development. KEGG enrichment analysis indicated that differentially upregulated mRNAs were mainly enriched in signal pathways such as insulin secretion
oxidative phosphorylation
and Parkinson's disease
while those down-regulated ones in signal pathways such as neuroactive ligand receptor interactions
calcium signaling pathways
tyrosine metabolism and phenylalanine metabolism. CeRNA network displayed that the circRNA_45921/miR-34c-5p/Eef2k regulatory network may play a role in the functioning of IAPP.
Conclusion
2
Intraperitoneal injection of IAPP alters the expression profiles of circRNA and mRNA in the brain tissues of AD mice and WT mice. Differentially expressed Paip2
Cdon
Ttr
and circRNA_45921/miR-34c-5p/Eef2k regulatory network may have regulatory roles in IAPP regulating the development of AD.
关键词
Keywords
references
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