Altered microRNA expression in patients with sarcoidosis

Main Article Content

Rajen Morar
Caroline Dickens
Therese Dix-Peek
Raquel Duarte
Charles Feldman


Sarcoidosis, MicroRNA, miRNA



Sarcoidosis is a granulomatous multisystem disease of uncertain aetiology. The disease has major inflammatory and immune components; however, the immunopathogenesis is not well understood. Micro ribonucleic acids (microRNAs) are classes of miniature, single-stranded, non-coding RNAs. Their key recognised role includes mediating the silencing of target genes post-transcriptionally. Recently, the role of miRNAs has gained interest in numerous disorders, suggested as being involved in pathogenesis of those diseases and acting as disease markers. Very little is known about the role of miRNAs in sarcoidosis, with nothing known regarding miRNAs in South African patients. The main objective, therefore, was to investigate the serum expression of approximately 800 miRNAs in patients with sarcoidosis compared with race-, age- and gender-matched healthy controls.


A total of six patients and six matched controls participated in this study. Whole blood samples were collected in EDTA tubes, processed and the plasma retained. RNA was extracted from the stored plasma samples using the QIAGEN miRNeasy Mini Kit® and concentrated using a salt-ethanol precipitation. The extracted miRNA was profiled using an nCounter® miRNA human v3 expression assay and data analysed using the nSolver™ Analysis Software.


After excluding one sample/control pair because of cellular RNA contamination, the remaining five patient and five matched control samples were analysed, and 145 miRNAs were found to be potentially differentially expressed. On applying a Bonferroni correction, the only miRNA that was significantly different was miRNA let-7a-5p, which was significantly overexpressed (141-fold change; p<0.0003) in patients compared with controls.


This is the first miRNA report of differentially expressed miRNAs in the serum of patients with sarcoidosis and matched healthy controls in South Africa. The results obtained suggest that miRNAs may play a role in sarcoidosis pathogenesis. Whether these molecules have diagnostic or prognostic implications, needs future studies recruiting larger patient cohorts.

Abstract 358 | PDF Downloads 330


1. Ranganathan K, Sivasankar V: MicroRNAs-Biology and clinical applications. J Oral Maxillofac Pathol. 2014; 18:229–34. doi: 10.4103/0973-029X.140762.
2. Zampetaki A, Mayr M: Analytical challenges and technical limitations in assessing circulating miRNAs. Thromb Haemost. 2012; 108:592–98. doi: 10.1160/TH12-02-0097.
3. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al.: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008; 105:10513–18. doi: 10.1073/pnas.0804549105.
4. Ciesla M, Skrzypek K, Kozakowska M, Loboda A, Jozkowicz A, Dulak J: MicroRNAs as biomarkers of disease onset. Anal Bioanal Chem. 2011; 401:2051–61. doi: 10.1007/s00216-011-5001-8.
5. Crouser ED, Julian MW, Crawford M, Shao G, Yu L, Planck SR, et al.: Differential expression of microRNA and predicted targets in pulmonary sarcoidosis. Biochem Bioph Res Co. 2012; 417:886–91. doi: 10.1016/j.bbrc.2011.12.068.
6. Maertzdorf J, Weiner J, Mollenkopf H-J, Network Tb, Bauer T, Prasse A, et al.: Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc Natl Acad Sci. 2012; 109:7853–58. doi: 10.1073/pnas.1121072109.
7. Jazwa A, Kasper L, Bak M, Sobczak M, Szade K, Jozkowicz A, et al.: Differential inflammatory microRNA and cytokine expression in pulmonary sarcoidosis. Arch Immunol Ther Exp. 2015; 63:139–46. doi: 10.1007/s00005-014-0315-9.
8. Hunninghake G, Costabel U, Ando M, Baughman R, Cordier J, Du Bois R, et al.: ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999; 16:149–73.
9. Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995; 57:289–300.
10. Lu T-P, Lee C-Y, Tsai M-H, Chiu Y-C, Hsiao CK, Lai L-C, et al.: miRSystem: an integrated system for characterizing enriched functions and pathways of microRNA targets. PLoS One. 2012; 7:e42390. doi: 10.1371/journal.pone.0042390.
11. Lee H, Han S, Kwon CS, Lee D: Biogenesis and regulation of the let-7 miRNAs and their functional implications. Protein Cell. 2016; 7:100–13. doi: 10.1007/s13238-015-0212-y.
12. Bonham CA: Biomarkers in sarcoidosis: can microRNAs fill the gap? Am J Respir Cell Mol Biol. 2018:1–2. doi: 10.1165/rcmb.2017-0344ED.
13. Salamo O, Mortaz E, Mirsaeidi M: Noncoding RNAs: new players in pulmonary medicine and sarcoidosis. Am J Respir Cell Mol Biol. 2018; 58:147–56. doi: 10.1165/rcmb.2017-0196TR.
14. Yamashita R, Sato M, Kakumu T, Hase T, Yogo N, Maruyama E, et al.: Growth inhibitory effects of miR‐221 and miR‐222 in non‐small cell lung cancer cells. Cancer Med. 2015; 4:551–64. doi: 10.1002/cam4.412.
15. Pattnaik B, Madan K, Mohan A, Mittal S: MicroRNAs in lung disease: a focus on sarcoidosis. Chest. 2020; 158:828. doi: 10.1016/j.chest.2020.01.057.
16. Ascoli C, Huang Y, Schott C, Turturice BA, Metwally A, Perkins DL, et al.: A circulating microRNA signature serves as a diagnostic and prognostic indicator in sarcoidosis. Am J Respir Cell Mol Biol. 2018; 58:40–54. doi: 10.1165/rcmb.2017-0207OC.
17. Kiszałkiewicz J, Piotrowski WJ, Pastuszak-Lewandoska D, Górski P, Antczak A, Górski W, et al.: Altered miRNA expression in pulmonary sarcoidosis. BMC Medical Genet. 2016; 17:2. doi: 10.1186/s12881-016-0266-6.
18. Zhou T, Casanova N, Pouladi N, Wang T, Lussier Y, Knox KS, et al.: Identification of Jak-STAT signaling involvement in sarcoidosis severity via a novel microRNA-regulated peripheral blood mononuclear cell gene signature. Sci Rep. 2017; 7:1–9. doi: 10.1038/s41598-017-04109-6.
19. Novosadova E, Chabronova A, Kolek V, Petrek M, Navratilova Z: The serum expression of selected miRNAs in pulmonary sarcoidosis with/without Löfgren’s syndrome. Mediators Inflamm. 2016; 2016:1–12. doi: 10.1155/2016/1246129.
20. Fujiwara W, Kato Y, Hayashi M, Sugishita Y, Okumura S, Yoshinaga M, et al.: Serum microRNA-126 and-223 as new-generation biomarkers for sarcoidosis in patients with heart failure. J Cardiol. 2018; 72:452–57. doi: 10.1016/j.jjcc.2018.06.004.
21. Asakage M, Usui Y, Nezu N, Shimizu H, Tsubota K, Yamakawa N, et al.: Comprehensive miRNA analysis using serum from patients with noninfectious uveitis. Investig Ophthalmol Vis Sci. 2020; 61:4–4. doi: 10.1167/iovs.61.11.4.
22. Ebrahimi G, Zhang C, Tian R, Urdaneta G, Griswold A, Mirsaeidi M: Serum versus peripheral blood mononuclear cells (PBMCs): different microRNA profiles in sarcoidosis patients. B35. Sarcoidosis Clinical and Mechanistic Studies, American Thoracic Society. 2020, pp. A3104–A3104.
23. Pattnaik B, Sryma P, Mittal S, Agrawal A, Guleria R, Madan K: MicroRNAs in pulmonary sarcoidosis: A systematic review. Respir Investig. 2020; 58:232–38. doi: 10.1016/j.resinv.2020.02.008.
24. Turchinovich A, Weiz L, Langheinz A, Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011; 39:7223–33. doi: 10.1093/nar/gkr254.
25. Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136:215–33. doi: 10.1016/j.cell.2009.01.002.
26. Sell SL, Widen SG, Prough DS, Hellmich HL. Principal component analysis of blood microRNA datasets facilitates diagnosis of diverse diseases. PLoS One. 2020 Jun 5;15(6):e0234185. doi: 10.1371/journal.pone.0234185.