Evaluation of Serum Levels of MicroRNA-200C and ACE2 Gene Expression in Severe and Mild Phases of Patients with COVID-19
Abstract
The role of microRNA (miR)200c-3p in regulating ACE2 gene expression in viral and bacterial respiratory diseases has been established. Since ACE2 reduces the acute inflammatory effects in lung diseases and acts as a coronavirus receptor to invade the lung cells, this study investigates the relationship between miR-200c-3p and ACE2 expression in COVID -19 patients.
In this study, COVID-19 patients were divided into two groups: mild phase (PCR-positive and mild symptoms) and severe phase (PCR-positive with acute pulmonary symptoms and inflammation). Then, the subjects' demographic, clinical, and paraclinical characteristics were recorded using a prepared checklist. Total RNA was isolated from all samples according to the Trizol kit protocol to evaluate gene expression. Subsequently, the extracted product was analysed for miR-200c expression and ACE2 target gene expression by real-time PCR.
The results of the checklist data showed that smoking, cough, and the factors ESR and HCT were statistically significant between the two groups of patients in the mild and acute phases. Also, the mean expression of the miR-200c gene in the mild and acute patients was 1.87±0.70 and 1.87±0.62, respectively, which was not statistically significant. Still, the mean expression of the ACE2 gene, which was 3.96±0.76 and 3.28±0.52 in the mild and acute disease groups, respectively, showed a significant difference between the two groups.
This study showed that the expression levels of ACE2 were significantly reduced in people with severe inflammation compared to people with mild inflammation.
1. Adhikari SP, Meng S, Wu Y-J, Mao Y-P, Ye R-X, Wang Q-Z, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty. 2020;9(1):1-12.
2. Di Gennaro F, Pizzol D, Marotta C, Antunes M, Racalbuto V, Veronese N, et al. Coronavirus diseases (COVID-19) current status and future perspectives: a narrative review. Int J Environ Res Public Health. 2020;17(8):2690-8.
3. Durham AL, Caramori G, Chung KF, Adcock IM. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Transl Res. 2016;167(1):192-203.
4. Xu Z-S, Shu T, Kang L, Wu D, Zhou X, Liao B-W, et al. Temporal profiling of plasma cytokines, chemokines, and growth factors from mild, severe and fatal COVID-19 patients. Signal Transduct Target Ther. 2020;5(1):1-3.
5. Alipour S, Sakhinia E, Khabbazi A, Samadi N, Babaloo Z, Azad M, et al. Methylation status of interleukin-6 gene promoter in patients with behcet's disease. Reumatol Clin. 2020;16(3):229-34.
6. Chen L, Wang G, Tan J, Cao Y, Long X, Luo H, et al. Scoring cytokine storm by the levels of MCP-3 and IL-8 accurately distinguished COVID-19 patients with high mortality. Signal Transduct Target Ther. 2020;5(1):1-3.
7. Farhadi J, Nouri M, Khabbazi A, Samadi N, Babaloo Z, Azad M, et al. Analysis of methylation and expression profile of Foxp3 gene in patients with Behçet’s syndrome. Iran J Allergy Asthma Immunol. 2020:1-8.
8. Abdi A, Khabazi A, Sakhinia E, Alipour S, Talei M, Babaloo Z. Evaluation of SOCS1 methylation in patients with Behcet’s disease. Immunol Lett. 2018;203(12):15-20.
9. Zhang X, Li S, Niu S. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020;96(1137):403-7.
10. Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation. 2021;44(1):13-34.
11. Jadideslam G, Ansarin K, Sakhinia E, Alipour S, Pouremamali F, Khabbazi A. The MicroRNA‐326: Autoimmune diseases, diagnostic biomarker, and therapeutic target. J Cell Physiol. 2018;233(12):9209-22.
12. Ahmadi M, Yousefi M, Abbaspour‐Aghdam S, Dolati S, Aghebati-Maleki L, Eghbal‐Fard S, et al. Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet’s disease. J Cell Physiol. 2019;234(4):3985-94.
13. Kolahi S, Farajzadeh M-J, Alipour S, Abhari A, Farhadi J, Bahavarnia N, et al. Determination of mir-155 and mir-146a expression rates and its association with expression level of TNF-α and CTLA4 genes in patients with Behcet’s disease. Immunol Lett. 2018;204:55-9.
14. Shahriar A, Shiva GG-a, Ghader B, Farhad J, Hosein A, Parsa H. The dual role of mir-146a in metastasis and disease progression. Biomed Pharmacother. 2020;126:110099.
15. Jadideslam G, Ansarin K, Sakhinia E, Babaloo Z, Abhari A, Alipour S, et al. Expression levels of miR-21, miR-146b and miR-326 as potential biomarkers in Behcet's disease. Biomark Med. 2019;13(16):1339-48.
16. Ghavami A, Roshanravan N, Alipour S, Barati M, Mansoori B, Ghalichi F, et al. Assessing the effect of high performance inulin supplementation via KLF5 mRNA expression in adults with type 2 diabetes: a randomized placebo controlled clinical trail. Adv Pharm Bull. 2018;8(1):39.
17. Oglesby IK, McElvaney NG, Greene CM. MicroRNAs in inflammatory lung disease-master regulators or target practice? Respir Res. 2010;11(1):1-13.
18. Liu Q, Du J, Yu X, Xu J, Huang F, Li X, et al. miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov. 2017;3(1):1-17.
19. El Kholy A, Mostafa N, Ali A, Soliman M, El-Sherbini S, Ismail R, et al. The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season. Eur J Clin Microbiol Infect Dis. 2016;35(10):1607-13.
20. Mutlu M, Raza U, Saatci Ö, Eyüpoğlu E, Yurdusev E, Şahin Ö. miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med. 2016;94(6):629-44.
21. Bellae Papannarao J, Schwenke DO, Manning P, Katare R. Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity. Int J Obes. 2021;12(3):1-4.
22. Patel VB, Zhong J-C, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circ Res. 2016;118(8):1313-26.
23. Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014;5(1):1-7.
24. Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R, et al. MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol. 2020;148:46-9.
25. Roca-Ho H, Riera M, Palau V, Pascual J, Soler MJ. Characterization of ACE and ACE2 expression within different organs of the NOD mouse. Int J Mol Sci. 2017;18(3):563.
26. Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020;324(2):168-77.
27. AlGhatrif M, Cingolani O, Lakatta EG. The dilemma of coronavirus disease 2019, aging, and cardiovascular disease: insights from cardiovascular aging science. JAMA Cardiol. 2020;5(7):747-8.
28. Fagyas M, Bánhegyi V, Úri K, Enyedi A, Lizanecz E, Mányiné IS, et al. Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients. Geroscience. 2021:1-16.
29. Pimenta R, Viana NI, Dos Santos GA, Candido P, Guimarães VR, Romão P, et al. MiR-200c-3p expression may be associated with worsening of the clinical course of patients with COVID-19. Mol Biol Res Commun. 2021;10(3):141.
30. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
2. Di Gennaro F, Pizzol D, Marotta C, Antunes M, Racalbuto V, Veronese N, et al. Coronavirus diseases (COVID-19) current status and future perspectives: a narrative review. Int J Environ Res Public Health. 2020;17(8):2690-8.
3. Durham AL, Caramori G, Chung KF, Adcock IM. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Transl Res. 2016;167(1):192-203.
4. Xu Z-S, Shu T, Kang L, Wu D, Zhou X, Liao B-W, et al. Temporal profiling of plasma cytokines, chemokines, and growth factors from mild, severe and fatal COVID-19 patients. Signal Transduct Target Ther. 2020;5(1):1-3.
5. Alipour S, Sakhinia E, Khabbazi A, Samadi N, Babaloo Z, Azad M, et al. Methylation status of interleukin-6 gene promoter in patients with behcet's disease. Reumatol Clin. 2020;16(3):229-34.
6. Chen L, Wang G, Tan J, Cao Y, Long X, Luo H, et al. Scoring cytokine storm by the levels of MCP-3 and IL-8 accurately distinguished COVID-19 patients with high mortality. Signal Transduct Target Ther. 2020;5(1):1-3.
7. Farhadi J, Nouri M, Khabbazi A, Samadi N, Babaloo Z, Azad M, et al. Analysis of methylation and expression profile of Foxp3 gene in patients with Behçet’s syndrome. Iran J Allergy Asthma Immunol. 2020:1-8.
8. Abdi A, Khabazi A, Sakhinia E, Alipour S, Talei M, Babaloo Z. Evaluation of SOCS1 methylation in patients with Behcet’s disease. Immunol Lett. 2018;203(12):15-20.
9. Zhang X, Li S, Niu S. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020;96(1137):403-7.
10. Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation. 2021;44(1):13-34.
11. Jadideslam G, Ansarin K, Sakhinia E, Alipour S, Pouremamali F, Khabbazi A. The MicroRNA‐326: Autoimmune diseases, diagnostic biomarker, and therapeutic target. J Cell Physiol. 2018;233(12):9209-22.
12. Ahmadi M, Yousefi M, Abbaspour‐Aghdam S, Dolati S, Aghebati-Maleki L, Eghbal‐Fard S, et al. Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet’s disease. J Cell Physiol. 2019;234(4):3985-94.
13. Kolahi S, Farajzadeh M-J, Alipour S, Abhari A, Farhadi J, Bahavarnia N, et al. Determination of mir-155 and mir-146a expression rates and its association with expression level of TNF-α and CTLA4 genes in patients with Behcet’s disease. Immunol Lett. 2018;204:55-9.
14. Shahriar A, Shiva GG-a, Ghader B, Farhad J, Hosein A, Parsa H. The dual role of mir-146a in metastasis and disease progression. Biomed Pharmacother. 2020;126:110099.
15. Jadideslam G, Ansarin K, Sakhinia E, Babaloo Z, Abhari A, Alipour S, et al. Expression levels of miR-21, miR-146b and miR-326 as potential biomarkers in Behcet's disease. Biomark Med. 2019;13(16):1339-48.
16. Ghavami A, Roshanravan N, Alipour S, Barati M, Mansoori B, Ghalichi F, et al. Assessing the effect of high performance inulin supplementation via KLF5 mRNA expression in adults with type 2 diabetes: a randomized placebo controlled clinical trail. Adv Pharm Bull. 2018;8(1):39.
17. Oglesby IK, McElvaney NG, Greene CM. MicroRNAs in inflammatory lung disease-master regulators or target practice? Respir Res. 2010;11(1):1-13.
18. Liu Q, Du J, Yu X, Xu J, Huang F, Li X, et al. miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov. 2017;3(1):1-17.
19. El Kholy A, Mostafa N, Ali A, Soliman M, El-Sherbini S, Ismail R, et al. The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season. Eur J Clin Microbiol Infect Dis. 2016;35(10):1607-13.
20. Mutlu M, Raza U, Saatci Ö, Eyüpoğlu E, Yurdusev E, Şahin Ö. miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med. 2016;94(6):629-44.
21. Bellae Papannarao J, Schwenke DO, Manning P, Katare R. Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity. Int J Obes. 2021;12(3):1-4.
22. Patel VB, Zhong J-C, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circ Res. 2016;118(8):1313-26.
23. Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014;5(1):1-7.
24. Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R, et al. MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol. 2020;148:46-9.
25. Roca-Ho H, Riera M, Palau V, Pascual J, Soler MJ. Characterization of ACE and ACE2 expression within different organs of the NOD mouse. Int J Mol Sci. 2017;18(3):563.
26. Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020;324(2):168-77.
27. AlGhatrif M, Cingolani O, Lakatta EG. The dilemma of coronavirus disease 2019, aging, and cardiovascular disease: insights from cardiovascular aging science. JAMA Cardiol. 2020;5(7):747-8.
28. Fagyas M, Bánhegyi V, Úri K, Enyedi A, Lizanecz E, Mányiné IS, et al. Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients. Geroscience. 2021:1-16.
29. Pimenta R, Viana NI, Dos Santos GA, Candido P, Guimarães VR, Romão P, et al. MiR-200c-3p expression may be associated with worsening of the clinical course of patients with COVID-19. Mol Biol Res Commun. 2021;10(3):141.
30. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
| Files | ||
| Issue | Vol 21 No 3 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i3.9799 | |
| Keywords | ||
| ACE2 protein miR200c, human Immune system Inflammation | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Sodagar H, Khadem Ansari MH, Asghari R, Alipour S. Evaluation of Serum Levels of MicroRNA-200C and ACE2 Gene Expression in Severe and Mild Phases of Patients with COVID-19. Iran J Allergy Asthma Immunol. 2022;21(3):254-262.
