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

• DOI: 10.1371/journal.pone.0283589
• Publication Date: 2023-04-13T17:45:21Z
• Authors: Hassan Ayaz; Nouman Aslam; Faryal Mehwish Awan; Rabea Basri; Bisma Rauff; Badr Alzahrani; Muhammad Arif; Aqsa Ikram; Ayesha Obaid; Anam Naz; Sadiq Noor Khan; Burton B. Yang; Azhar Nazir
• Keywords: FOS: Computer and information sciences; Cancer Research; MicroRNA Regulation in Cancer and Development; Bioinformatics; Science; Gene; Computational biology; Biochemistry, Genetics and Molecular Biology; Genetics; Humans; Regulation of gene expression; RNA, Messenger; Biogenesis and Functions of Circular RNAs; Precision Medicine; Non-coding RNA; Molecular Biology; Biology; Circular RNA; microRNA; SARS-CoV-2; Messenger RNA; Q; Gene regulatory network; R; COVID-19; Life Sciences; RNA, Circular; Competing endogenous RNA; 3. Good health; MicroRNAs; FOS: Biological sciences; Long non-coding RNA; Medicine; RNA; Epigenetics; Gene expression; Circular RNAs; Research Article

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.