Long Noncoding RNAs as Emerging Regulators of COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.

microRNAs and Inflammatory Immune Response in SARS-CoV-2 Infection: A Narrative Review

“…These results suggested a potential pathogenic hypothesis for the aberrant cytokine production, as well as leukocyte differentiation and migration. The study also supports recent evidence indicating that lncRNAs may influence miRNA activity, highlighting the presence of an intricate endogenous RNA network between lncRNAs, mRNAs and miRNAs [46,47].…”

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis

“…Lastly, our observation that CTSL, a protein crucial for COVID-19 viral entry is upregulated across multiple cell types in severe patients provides a potential initial mechanism for the induction of the NEAT1 and MALAT1 mediated inflammatory state through increased efficiency of viral entry [ 72 ]. Recently, additional independent evidence and reviews have emerged highlighting expression of NEAT1 and MALAT1 in both in vitro and in vivo samples of COVID-19 infection [ 83 – 86 ]. These additional studies provide further evidence that the patterns of lncRNA expression presented in this study are highly associated with COVID-19 related inflammation.…”

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

“…Negative regulators, such as suppressors of cytokine signaling (SOCS), USP 18, and STAT3, may help IFN-induced cells to return to cellular homeostasis. Such cytokine responses induce the host's immune system to clear the virus; however, if the immune system is overactivated, the cytokines might infiltrate the lung tissue and develop a cytokine storm leading to acute respiratory distress syndrome (ARDS) [6][7][8][9]. The escape of the antiviral response of the host is mediated through alteration of transcription of the host PCG as well as non-coding RNA genes; a detailed description of altered gene expression is discussed in the following sections [4,5].…”

“…Diverse biological processes and pathways associated with deregulated lncRNA in SARS-CoV-2 infection have been reported and reviewed. These pathways include oxidative stress, immune responses [42], NLRP3 inflammasome [43,44], TNF signaling pathway, IL-17 signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, Influenza A, chemokine signaling pathway, RIG-I-like receptor signaling pathway, MAPK signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, AGE-RAGE signaling pathway in diabetic complications, FoxO signaling pathway, apoptosis, epithelial cell signaling in Helicobacter pylori infection and cellular senescence [35], viral defense response, innate immune response, and inflammatory response [9].…”