The Regulation of Messenger RNAs and Biological Pathways by Long Non-Coding RNAs and Circular RNAs in Ischemic Stroke

Abstract

Our aim was to evaluate the regulation of messenger RNAs (mRNAs) and biological pathways by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in ischemic stroke. We employed weighted gene co-expression network analysis (WGCNA) to construct two co-expression networks for mRNAs with circRNAs and lncRNAs, respectively, to investigate their association with ischemic stroke. We compared the overlap of mRNAs and biological pathways in the stroke-associated modules of the two networks. Furthermore, we validated the association of key non-coding RNAs with the risk of ischemic stroke and poor prognosis using quantitative real-time polymerase chain reaction. Ischemic stroke patients exhibited lower eigengene expression in the turquoise module associated with lncRNAs and mRNAs, as well as in the turquoise, red, and greenyellow modules associated with circRNAs and mRNAs in ischemic stroke. In the lncRNA-mRNA network and circRNA-mRNA network, we observed a significant overlap of the 5126 mRNAs (P < 0.001) and 51 biological pathways (P < 0.001), respectively. Among the ten key non-coding RNAs, lnc-TPRG1-AS1, lnc-GUK1, and hsa_circ_RELL1 were significantly increased (P < 0.05), while hsa_circ_ZBTB20 and hsa_circ_ERBB2 were significantly decreased (P < 0.05) in ischemic stroke. Additionally, ischemic stroke patients with poor functional outcome had significantly lower levels of hsa_circ_ZBTB20 and hsa_circ_ERBB2 compared to those with favorable prognosis (P < 0.05). Our findings suggest lncRNAs and circRNAs display similar biological functions in ischemic stroke. Key non-coding RNAs may be associated with the risk and clinical prognosis of ischemic stroke. These results warrant further validation in the future studies.