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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Research Article

The Impact of lncRNA-GAS5/miRNA-200/ACE2 Molecular Pathway on the Severity of COVID-19

Author(s): Ghada Ayeldeen, Olfat G. Shaker, Eman Amer, Mai A. Zaafan, Mohamed R. Herzalla, Mofida A. Keshk and Amr M. Abdelhamid*

Volume 31, Issue 9, 2024

Published on: 12 July, 2023

Page: [1142 - 1151] Pages: 10

DOI: 10.2174/0929867330666230515144133

Price: $65

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2), which is responsible for coronavirus disease (COVID-19), potentially has severe adverse effects, leading to public health crises worldwide. In COVID-19, deficiency of ACE-2 is linked to increased inflammation and cytokine storms via increased angiotensin II levels and decreased ACE-2/Mas receptor axis activity. MiRNAs are small sequences of noncoding RNAs that regulate gene expression by binding to the targeted mRNAs. MiR-200 dysfunction has been linked to the development of ARDS following acute lung injury and has been proposed as a key regulator of ACE2 expression. LncRNA growth arrest-specific transcript 5 (GAS5) has been recently studied for its modulatory effect on the miRNA-200/ACE2 axis.

Objective: The current study aims to investigate the role of lncRNA GAS5, miRNA-200, and ACE2 as new COVID-19 diagnostic markers capable of predicting the severity of SARS-CoV-2 complications.

Methods: A total of 280 subjects were classified into three groups: COVID-19-negative controls (n = 80), and COVID-19 patients (n=200) who required hospitalization were classified into two groups: group (2) moderate cases (n = 112) and group (3) severe cases (n = 88).

Results: The results showed that the serum GAS5 expression was significantly down-expressed in COVID-19 patients; as a consequence, the expression of miR-200 was reported to be overexpressed and its targeted ACE2 was down-regulated. The ROC curve was drawn to examine the diagnostic abilities of GAS5, miR-200, and ACE2, yielding high diagnostic accuracy with high sensitivity and specificity.

Conclusion: lncRNA-GAS5, miRNA-200, and ACE2 panels presented great diagnostic potential as they demonstrated the highest diagnostic accuracy for discriminating moderate COVID-19 and severe COVID-19 cases.

Keywords: COVID-19, ACE2, lncRNA-GAS5, miRNA-200, long non-coding RNAs (lncRNAs), ROC.

[1]
Chen, J.M. Novel statistics predict the COVID-19 pandemic could terminate in 2022. J. Med. Virol., 2022, 94(6), 2845-2848.
[http://dx.doi.org/10.1002/jmv.27661] [PMID: 35150458]
[2]
Bozgeyik, I. Therapeutic potential of miRNAs targeting SARS-CoV-2 host cell receptor ACE2. Meta Gene, 2021, 27, 100831.
[http://dx.doi.org/10.1016/j.mgene.2020.100831] [PMID: 33224734]
[3]
Blume, C.; Jackson, C.L.; Spalluto, C.M.; Legebeke, J.; Nazlamova, L.; Conforti, F.; Perotin, J.M.; Frank, M.; Butler, J.; Crispin, M.; Coles, J.; Thompson, J.; Ridley, R.A.; Dean, L.S.N.; Loxham, M.; Reikine, S.; Azim, A.; Tariq, K.; Johnston, D.A.; Skipp, P.J.; Djukanovic, R.; Baralle, D.; McCormick, C.J.; Davies, D.E.; Lucas, J.S.; Wheway, G.; Mennella, V. A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection. Nat. Genet., 2021, 53(2), 205-214.
[http://dx.doi.org/10.1038/s41588-020-00759-x] [PMID: 33432184]
[4]
Sajdel-Sulkowska, E.M. A dual-route perspective of SARS-CoV-2 infection: Lung- vs. gut-specific effects of ACE-2 deficiency. Front. Pharmacol., 2021, 12, 684610.
[http://dx.doi.org/10.3389/fphar.2021.684610] [PMID: 34177593]
[5]
Magrone, T.; Magrone, M.; Jirillo, E. Focus on receptors for coronaviruses with special reference to Angiotensin- Converting Enzyme 2 as a Potential Drug Target - A Perspective. Endocr. Metab. Immune Disord. Drug Targets, 2020, 20(6), 807-811.
[http://dx.doi.org/10.2174/22123873MTA2iMTYgx] [PMID: 32338224]
[6]
Yalcin, H.C.; Sukumaran, V.; Al-Ruweidi, M.K.A.A.; Shurbaji, S. Do changes in ACE-2 expression affect SARS-CoV-2 virulence and related complications: A closer look into membrane-bound and soluble forms. Int. J. Mol. Sci., 2021, 22(13), 6703.
[http://dx.doi.org/10.3390/ijms22136703] [PMID: 34201415]
[7]
Abdelhamid, A.M.; Selim, A.; Zaafan, M.A. The hepatoprotective effect of piperine against thioacetamide-induced liver fibrosis in mice: The involvement of miR-17 and TGF-β/Smads pathways. Front. Mol. Biosci., 2021, 8, 754098.2021,
[8]
Liu, Q.; Du, J.; Yu, X.; Xu, J.; Huang, F.; Li, X.; Zhang, C.; Li, X.; Chang, J.; Shang, D.; Zhao, Y.; Tian, M.; Lu, H.; Xu, J.; Li, C.; Zhu, H.; Jin, N.; Jiang, C. miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov., 2017, 3(1), 17021.
[http://dx.doi.org/10.1038/celldisc.2017.21] [PMID: 28690868]
[9]
Abdelhamid, A.M.; El Deeb, M.; Zaafan, M.A. The protective effect of xanthenone against LPS-induced COVID-19 acute respiratory distress syndrome (ARDS) by modulating the ACE2/Ang-1-7 signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2022, 26(14), 5285-5296.
[PMID: 35916829]
[10]
Shaker, O.; Ayeldeen, G.; Abdelhamid, A. The impact of single nucleotide polymorphism in the long non-coding MEG3 gene on MicroRNA-182 and MicroRNA-29 expression levels in the development of breast cancer in Egyptian women. Front. Genet., 2021, 12, 683809.
[http://dx.doi.org/10.3389/fgene.2021.683809] [PMID: 34421993]
[11]
Li, H.B.; Zi, P.P.; Shi, H.J.; Gao, M.; Sun, R.Q. Role of signaling pathway of long non-coding RNA growth arrest-specific transcript 5/microRNA-200c-3p/angiotensin converting enzyme 2 in the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome. Chin. Med. J., 2018, 98(41), 3354-3359.
[PMID: 30440128]
[12]
Hegazy, M.A.; Lithy, R.M.; Abdel-Hamid, H.M.; Wahba, M.; Ashoush, O.A.; Hegazy, M.T.; El-Din Ibrahim, M.H.; Abdelfatah, D.; Abdelghani, A. COVID-19 disease outcomes: Does gastrointestinal burden play a role? Clin. Exp. Gastroenterol., 2021, 14, 199-207.
[http://dx.doi.org/10.2147/CEG.S297428] [PMID: 34079323]
[13]
Wasilewski, P.; Mruk, B.; Mazur, S.; Półtorak-Szymczak, G.; Sklinda, K.; Walecki, J. COVID-19 severity scoring systems in radiological imaging-a review. Pol. J. Radiol., 2020, 85(1), 361-368.
[http://dx.doi.org/10.5114/pjr.2020.98009] [PMID: 32817769]
[14]
Duzgun, S.A.; Durhan, G.; Demirkazik, F.B.; Akpinar, M.G.; Ariyurek, O.M. COVID-19 pneumonia: The great radiological mimicker. Insights Imaging, 2020, 11(1), 118.
[http://dx.doi.org/10.1186/s13244-020-00933-z] [PMID: 33226521]
[15]
Takahashi, Y.; Hayakawa, A.; Sano, R.; Fukuda, H.; Harada, M.; Kubo, R.; Okawa, T.; Kominato, Y. Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19. Sci. Rep., 2021, 11(1), 3379.
[http://dx.doi.org/10.1038/s41598-021-82970-2] [PMID: 33564039]
[16]
Mehandru, S.; Merad, M. Pathological sequelae of long-haul COVID. Nat. Immunol., 2022, 23(2), 194-202.
[http://dx.doi.org/10.1038/s41590-021-01104-y] [PMID: 35105985]
[17]
Long, B.; Carius, B.M.; Chavez, S.; Liang, S.Y.; Brady, W.J.; Koyfman, A.; Gottlieb, M. Clinical update on COVID-19 for the emergency clinician: Presentation and evaluation. Am. J. Emerg. Med., 2022, 54, 46-57.
[http://dx.doi.org/10.1016/j.ajem.2022.01.028] [PMID: 35121478]
[18]
Cousin, V.L.; Giraud, R.; Bendjelid, K. Pathophysiology of COVID-19: Everywhere you look you will see ACE2! Front. Med., 2021, 8, 694029.
[http://dx.doi.org/10.3389/fmed.2021.694029] [PMID: 34513868]
[19]
Sriram, K.; Insel, P.A. A hypothesis for pathobiology and treatment of COVID-19 : The centrality of ACE1 / ACE2 imbalance. Br. J. Pharmacol., 2020, 177(21), 4825-4844.
[http://dx.doi.org/10.1111/bph.15082] [PMID: 32333398]
[20]
Abdel-Nasser, Z.M.; Zaafan, M.A.; Abdelhamid, A.M. Modulation of the miR-122/Sirt-6/ACE2 axis on experimentally-induced myocardial infarction. Chem. Biol. Interact., 2023, 369, 110276.
[http://dx.doi.org/10.1016/j.cbi.2022.110276] [PMID: 36414029]
[21]
Colarusso, C.; Terlizzi, M.; Pinto, A.; Sorrentino, R. A lesson from a saboteur: High-MW kininogen impact in coronavirus-induced disease 2019. Br. J. Pharmacol., 2020, 177(21), 4866-4872.
[http://dx.doi.org/10.1111/bph.15154] [PMID: 32497257]
[22]
Liu, C.; Li, Y.; Guan, T.; Lai, Y.; Shen, Y.; Zeyaweiding, A.; Zhao, H.; Li, F.; Maimaiti, T. ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus. Cardiovasc. Diabetol., 2018, 17(1), 127.
[http://dx.doi.org/10.1186/s12933-018-0771-3] [PMID: 30227878]
[23]
Sayed, S. COVID-19 and diabetes; Possible role of polymorphism and rise of telemedicine. Prim. Care Diabetes, 2021, 15(1), 4-9.
[http://dx.doi.org/10.1016/j.pcd.2020.08.018] [PMID: 32912711]
[24]
Shaker, O.G. Circulating microRNA-944 and its target gene EPHA7 as a potential biomarker for colorectal cancer. Arch. Physiol. Biochem., 2022, 128(5), 1181-1187.
[25]
Zaafan, M.A.; Abdelhamid, A.M. The cardioprotective effect of microRNA-103 inhibitor against isoprenaline-induced myocardial infarction in mice through targeting FADD/RIPK pathway. Eur. Rev. Med. Pharmacol. Sci., 2021, 25(2), 837-844.
[PMID: 33577038]
[26]
Zaafan, M.A.; Abdelhamid, A.M. Dasatinib ameliorates thioacetamide-induced liver fibrosis: Modulation of miR-378 and miR-17 and their linked Wnt/β-catenin and TGF-β/smads pathways. J. Enzyme Inhib. Med. Chem., 2022, 37(1), 118-124.
[http://dx.doi.org/10.1080/14756366.2021.1995379] [PMID: 34894966]
[27]
Hoefel, G.; Tay, H.; Foster, P. MicroRNAs in lung diseases. Chest, 2019, 156(5), 991-1000.
[http://dx.doi.org/10.1016/j.chest.2019.06.008] [PMID: 31255581]
[28]
Elfert, A.Y. Implication of miR-122, miR-483, and miR-335 expression levels as potential signatures in HCV-related hepatocellular carcinoma (HCC) in Egyptian patients. Front. Mol. Biosci., 2022, 9
[29]
Rezaei, M.; Ziai, S.A.; Fakhri, S.; Pouriran, R. ACE2: Its potential role and regulation in severe acute respiratory syndrome and COVID-19. J. Cell. Physiol., 2021, 236(4), 2430-2442.
[http://dx.doi.org/10.1002/jcp.30041] [PMID: 32901940]

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