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绘制环状 RNA-miRNA-mRNA 调控轴鉴定 hsa_circ_0080942 和 hsa_circ_0080135 作为 SARS-CoV-2 感染的潜在治疗靶点。

Mapping CircRNA-miRNA-mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection.

机构信息

Department of Medical Lab Technology, The University of Haripur (UOH), Haripur, Khyber Pakhtunkhwa, Pakistan.

Department of Biomedical Engineering, University of Engineering and Technology (UET), Lahore, Narowal, Pakistan.

出版信息

PLoS One. 2023 Apr 13;18(4):e0283589. doi: 10.1371/journal.pone.0283589. eCollection 2023.

DOI:10.1371/journal.pone.0283589
PMID:37053191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10101458/
Abstract

Non-coding RNAs (ncRNAs) can control the flux of genetic information; affect RNA stability and play crucial roles in mediating epigenetic modifications. A number of studies have highlighted the potential roles of both virus-encoded and host-encoded ncRNAs in viral infections, transmission and therapeutics. However, the role of an emerging type of non-coding transcript, circular RNA (circRNA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been fully elucidated so far. Moreover, the potential pathogenic role of circRNA-miRNA-mRNA regulatory axis has not been fully explored as yet. The current study aimed to holistically map the regulatory networks driven by SARS-CoV-2 related circRNAs, miRNAs and mRNAs to uncover plausible interactions and interplay amongst them in order to explore possible therapeutic options in SARS-CoV-2 infection. Patient datasets were analyzed systematically in a unified approach to explore circRNA, miRNA, and mRNA expression profiles. CircRNA-miRNA-mRNA network was constructed based on cytokine storm related circRNAs forming a total of 165 circRNA-miRNA-mRNA pairs. This study implies the potential regulatory role of the obtained circRNA-miRNA-mRNA network and proposes that two differentially expressed circRNAs hsa_circ_0080942 and hsa_circ_0080135 might serve as a potential theranostic agents for SARS-CoV-2 infection. Collectively, the results shed light on the functional role of circRNAs as ceRNAs to sponge miRNA and regulate mRNA expression during SARS-CoV-2 infection.

摘要

非编码 RNA（ncRNAs）可以控制遗传信息的流动；影响 RNA 的稳定性，并在介导表观遗传修饰中发挥关键作用。许多研究强调了病毒编码和宿主编码 ncRNAs 在病毒感染、传播和治疗中的潜在作用。然而，环状 RNA（circRNA）作为一种新兴的非编码转录本，在严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染中的作用尚未得到充分阐明。此外，circRNA-miRNA-mRNA 调控轴的潜在致病作用尚未得到充分探索。本研究旨在全面绘制由 SARS-CoV-2 相关 circRNAs、miRNAs 和 mRNAs 驱动的调控网络，以揭示它们之间可能的相互作用和相互作用，从而探索 SARS-CoV-2 感染的可能治疗选择。通过系统的统一方法分析患者数据集，以探索 circRNA、miRNA 和 mRNA 的表达谱。基于细胞因子风暴相关 circRNAs 构建了 circRNA-miRNA-mRNA 网络，共形成 165 个 circRNA-miRNA-mRNA 对。本研究表明获得的 circRNA-miRNA-mRNA 网络具有潜在的调控作用，并提出两个差异表达的 circRNA hsa_circ_0080942 和 hsa_circ_0080135 可能作为 SARS-CoV-2 感染的潜在治疗剂。总之，这些结果揭示了 circRNAs 作为 ceRNA 在外泌体中吸附 miRNA 并调节 SARS-CoV-2 感染过程中 mRNA 表达的功能作用。

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