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Article

In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity

by
Sara H. A. Agwa
1,*,
Hesham Elghazaly
2,
Mahmoud Shawky El Meteini
3,
Sherif M. Shawky
1,4,5,*,
Marwa Ali
6,
Aya M. Abd Elsamee
7,
Safa Matbouly Sayed
8,
Nadine Sherif
6,
Howida M. Sharaf
9,
Mohamed A. Alhadidy
10 and
Marwa Matboli
1,6,*
1
Pathology and Molecular Genomics Unit of Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
2
Oncology Department, Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11382, Egypt
3
Department of General Surgery, School of Medicine, University of Ain Shams, Cairo 11591, Egypt
4
Biochemistry Department, Faculty of Pharmacy, Misr University for Science and Technology, Al-Motamayez District, P.O. BOX 77, 6th October City 12566, Egypt
5
Center of Genomics, Helmy Medical Institute, Zewail City of Science and Technology, Ahmed Zewail Road, October Gardens, 6th of October City 12578, Egypt
6
Medicinal Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
7
Biochemistry and Molecular Genomics Unit of Medical Ain Shams Research Institute (MASRI), Ain Shams University, Cairo 11591, Egypt
8
Pediatric Department, School of Medicine, Ain Shams University Hospitals, Cairo 11566, Egypt
9
Clinical & Molecular Pathology, Ain Shams University Hospitals, Cairo 11591, Egypt
10
Department of Anesthesiology, Intensive Care & Pain Management, Faculty of Medicine, Ain Shams University, Abbassia, Cairo 11591, Egypt
*
Authors to whom correspondence should be addressed.
Cells 2021, 10(11), 3098; https://doi.org/10.3390/cells10113098
Submission received: 21 September 2021 / Revised: 23 October 2021 / Accepted: 2 November 2021 / Published: 9 November 2021
(This article belongs to the Special Issue Role of Non-coding RNA in Health and Disease)
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Abstract

(1) Background: The coronavirus (COVID-19) pandemic is still a major global health problem, despite the development of several vaccines and diagnostic assays. Moreover, the broad symptoms, from none to severe pneumonia, and the various responses to vaccines and the assays, make infection control challenging. Therefore, there is an urgent need to develop non-invasive biomarkers to quickly determine the infection severity. Circulating RNAs have been proven to be potential biomarkers for a variety of diseases, including infectious ones. This study aimed to develop a genetic network related to cytokines, with clinical validation for early infection severity prediction. (2) Methods: Extensive analyses of in silico data have established a novel IL11RA molecular network (IL11RNA mRNA, LncRNAs RP11-773H22.4 and hsa-miR-4257). We used different databases to confirm its validity. The differential expression within the retrieved network was clinically validated using quantitative RT-PCR, along with routine assessment diagnostic markers (CRP, LDH, D-dimmer, procalcitonin, Ferritin), in100 infected subjects (mild and severe cases) and 100 healthy volunteers. (3) Results: IL11RNA mRNA and LncRNA RP11-773H22.4, and the IL11RA protein, were significantly upregulated, and there was concomitant downregulation of hsa-miR-4257, in infected patients, compared to the healthy controls, in concordance with the infection severity. (4) Conclusion: The in-silico data and clinical validation led to the identification of a potential RNA/protein signature network for novel predictive biomarkers, which is in agreement with ferritin and procalcitonin for determination of COVID-19 severity.
Keywords: circulating RNAs; bioinformatics; SARS-COV-2 infection severity prediction; interleukins genetic network; coding and non-coding RNAs; COVID-19 infection potential biomarker; IL11RA protein overexpression circulating RNAs; bioinformatics; SARS-COV-2 infection severity prediction; interleukins genetic network; coding and non-coding RNAs; COVID-19 infection potential biomarker; IL11RA protein overexpression

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MDPI and ACS Style

Agwa, S.H.A.; Elghazaly, H.; Meteini, M.S.E.; Shawky, S.M.; Ali, M.; Abd Elsamee, A.M.; Sayed, S.M.; Sherif, N.; Sharaf, H.M.; Alhadidy, M.A.; et al. In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity. Cells 2021, 10, 3098. https://doi.org/10.3390/cells10113098

AMA Style

Agwa SHA, Elghazaly H, Meteini MSE, Shawky SM, Ali M, Abd Elsamee AM, Sayed SM, Sherif N, Sharaf HM, Alhadidy MA, et al. In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity. Cells. 2021; 10(11):3098. https://doi.org/10.3390/cells10113098

Chicago/Turabian Style

Agwa, Sara H. A., Hesham Elghazaly, Mahmoud Shawky El Meteini, Sherif M. Shawky, Marwa Ali, Aya M. Abd Elsamee, Safa Matbouly Sayed, Nadine Sherif, Howida M. Sharaf, Mohamed A. Alhadidy, and et al. 2021. "In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity" Cells 10, no. 11: 3098. https://doi.org/10.3390/cells10113098

APA Style

Agwa, S. H. A., Elghazaly, H., Meteini, M. S. E., Shawky, S. M., Ali, M., Abd Elsamee, A. M., Sayed, S. M., Sherif, N., Sharaf, H. M., Alhadidy, M. A., & Matboli, M. (2021). In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity. Cells, 10(11), 3098. https://doi.org/10.3390/cells10113098

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