Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death‑related ceRNA network

Yiteng Cui; Xin Zhou; Pingping Meng; Shanshan Dong; Ziwei Wang; Tongye Liu; Xiaomin Liu; Yunteng Cui; Yuyang Wang; Qiang Wang

doi:10.3892/etm.2022.11616

Identifying potential therapeutic targets for ischemic stroke through immune infiltration analysis and construction of a programmed cell death‑related ceRNA network

Exp Ther Med. 2022 Sep 21;24(5):680. doi: 10.3892/etm.2022.11616. eCollection 2022 Nov.

Authors

Affiliations

¹ Department of Rehabilitation Medicine and Physiotherapy, Qingdao University of Medicine, Qingdao, Shandong 266071, P.R. China.
² Department of Rehabilitation Medicine, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
³ Department of Physical Therapy Program, Washington University of Medicine, St. Louis, MO 63110, USA.
⁴ Department of Rehabilitation and Health Care, Jinan Vocational College of Nursing, Jinan, Shandong 250102, P.R. China.

Abstract

The present study aimed to uncover the underlying mechanisms and potential intervention targets of ischemic stroke (IS). An immune cell infiltration analysis using CIBERSORT was performed on two stroke-related datasets from the Gene Expression Omnibus database to generate a competitive endogenous RNA (ceRNA) network. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict potential biological functions of the network. Differentially expressed genes in the ceRNA network and programmed cell death-related genes were intersected to obtain common genes for a stroke ceRNA network related to programmed cell death. These genes were further verified through a middle cerebral artery occlusion rat model using reverse transcription-quantitative PCR. This built a ceRNA regulatory network based on bioinformatic analysis. In addition to the biological functions extracted from the GO and KEGG enrichment analyses, it was discovered that long non-coding (lnc)RNA-mediated ceRNA regulatory pathways were associated with programmed cell death. This included five for apoptosis (lncRNA deleted in lymphocytic leukemia 2 like (DLEU2L)/micro (miR)-4500/sulfite oxidase, lncRNA DLEU2L/miR-4500/transforming growth factor β receptor III, lncRNA DLEU2L/miR-4500/BTB and CNC homology 1 (BACH1), lncRNA DLEU2L/miR-4500/zinc finger and BTB domain containing 5 and lncRNA LINC00266-1/miR-363-3p/zinc finger protein 354B and two for ferroptosis (lncRNA DLEU2L/miR-4500/ribo-nucleotide reductase regulatory subunit M2 and lncRNA DLEU2L/miR-4500/BACH1). Based on the aforementioned results, the present study provided potential approaches for bridging programmed cell death, immune infiltration and ceRNA regulatory networks in IS. The present study may provide novel insights into the clinical diagnosis and treatment of IS, and may improve the knowledge of the regulation of pathophysiological processes for IS.

Keywords: apoptosis; competitive endogenous RNA; ferroptosis; immune infiltration analysis; ischemic stroke; programmed cell death.

Grants and funding

Funding: This study was supported by the Natural Science Foundation of Shandong Province (grant nos. ZR2020MH282 and ZR2021QH143).