In Silico Identification of miRNA–lncRNA Interactions in Male Reproductive Disorder Associated with COVID-19 Infection

Abstract

Coronavirus disease 2019 (COVID-19), a global pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and transmembrane serine protease 2 (TMPRSS2) facilitates ACE2-mediated virus entry. Moreover, the expression of ACE2 in the testes of infertile men is higher than normal, which indicates that infertile men may be susceptible to be infected and SARS-CoV-2 may cause reproductive disorder through the pathway induced by ACE2 and TMPRSS2. Little is known about the pathway regulation of ACE2 and TMPRSS2 expression in male reproductive disorder. Since the regulation of gene expression is mediated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) at the post-transcriptional level, the aim of this study was to analyze the dysregulated miRNA–lncRNA interactions of ACE2 and TMPRSS2 in male reproductive disorder. Using bioinformatics analysis, we speculate that the predicted miRNAs including miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 as regulators of ACE2 and miR-204-5p as a modulator of TMPRSS2 are associated with male infertility. The lncRNAs with a tissue-specific expression for testis including GRM7-AS3, ARHGAP26-AS1, BSN-AS1, KRBOX1-AS1, CACNA1C-IT3, AC012361.1, FGF14-IT1, AC012494.1, and GS1-24F4.2 were predicted. The identified miRNAs and lncRNAs are proposed as potential biomarkers to study the possible association between COVID-19 and male infertility. This study encourages further studies of miRNA–lncRNA interactions to explain the molecular mechanisms of male infertility in COVID-19 patients.

miRNA expression in COVID-19

“… ( Sacconi et al, 2020 ) miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 Bioinformatics, in silico ACE2 expression The study indicates possible use of miRNAs in the diagnosis of male infertility after infection with SARS- CoV-2. ( Sabetian et al, 2021 ) miR-204-5p TMPRSS2 SARS-CoV-miR-029, miR-055, miR-084, miR-027, miR-005, miR-077, miR-060, miR-007 In silico Human genes Expression of human genes mediated by SARS CoV 2 miRNAs affects adaptive hypoxia, neuronal invasion, hormonal imbalances, and induction of cancer pathways. ( Roy et al, 2021 ) miR-146a, miR-155 Bioinformatics Patients with periodontitis and type2 diabetes ACE2 Increased miR 146a, miR 155 due to diabetes and periodontitis in the oral cavity upregulates angiotensin converting enzyme 2 expression and modulates the host antiviral response.…”

Potential Drugs Against COVID-19 Revealed By Gene Expression profile, Molecular Docking and Molecular Dynamic Simulation

“…In conclusion, we proposed several existing drugs with antiviral activity that, alone or in combination, could be considered as drugs against COVID-19. However, it is vital to better understand the clinicopathological features of COVID-19 to design treatment plans leading to favorable outcomes in SARS-CoV-2 infected patients [ 56 , 57 ].…”

Assessing the suitability of long non-coding RNAs as therapeutic targets and biomarkers in SARS-CoV-2 infection

“…For COVID-19, an abnormal expression pattern of lncRNAs related to T cell differentiation/activation could be a potential indicator for T-lymphopenia and requirement for modulating effector vs regulatory T cell balance, which could lead to better outcomes of in treatment and recovery ( Zheng et al, 2020 ). Moreover, some lncRNAs and miRNAs are also found to be associated with SARS-CoV-2 infection-induced male infertility/reproductive disorder, which is a less immediate outcome of the infection and these ncRNAs could serve as early diagnostic biomarkers, thus encouraging early treatment ( Sabetian et al, 2021 ).…”