Effect of amylin on expression profiles of circRNAs and mRNAs in brain tissue of Alzheimer's disease mice

Abstract

Objective 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 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 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 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.

Keywords

• alzheimer's disease
• amylin
• circrna
• mrna