Abstract

BackgroundIschemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke.MethodsRNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed.ResultsA total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained.ConclusionsThe results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

Highlights

  • IntroductionCircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke

  • Ischemic stroke is a disease with high rate of death and disability worldwide

  • Three models of Circular RNA (circRNA) regulating the expression of parental gene: (1) The intron-only ciRNA binds to elongating RNA Pol II and promotes host transcription in a cis-acting manner; (2) EIciRNA binds to U1 snRNP through specific RNARNA interaction between U1 snRNA and EIciRNA, and the EIciRNA-U1 snRNP complexes might interact with RNA Pol II transcription complex to promote host gene expression; (3) CircRNA shares some miRNA binding sites with 3’-UTR of the transcript from their parental gene, and CircRNA acts as miRNA sponge and increases the translations of the transcript from its parental gene [6]

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Summary

Introduction

CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. At present, there is no effective treatment available for cerebral ischemic diseases; this deficiency is Lacking 5’ caps and 3’ poly-A tails, circular RNAs (circRNAs) are resistant to RNaseR treatment (which degrades essentially all linear forms of RNAs), which makes circRNAs more stable than linear RNAs [4]. In. Wei et al BMC Neurology (2021) 21:370 addition, circRNAs are evolutionarily conserved among diverse species [4]. Wei et al BMC Neurology (2021) 21:370 addition, circRNAs are evolutionarily conserved among diverse species [4] These features enable circRNAs to perform a variety of physiological functions, including mediating alternative splicing of mRNAs, regulating the transcription of parental genes and binding to miRNAs as competing endogenous RNAs [5]. Three models of circRNA regulating the expression of parental gene: (1) The intron-only ciRNA binds to elongating RNA Pol II and promotes host transcription in a cis-acting manner; (2) EIciRNA binds to U1 snRNP through specific RNARNA interaction between U1 snRNA and EIciRNA, and the EIciRNA-U1 snRNP complexes might interact with RNA Pol II transcription complex to promote host gene expression; (3) CircRNA shares some miRNA binding sites with 3’-UTR of the transcript from their parental gene, and CircRNA acts as miRNA sponge and increases the translations of the transcript from its parental gene [6]

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