Nutr Res Pract.  2020 Aug;14(4):412-422. 10.4162/nrp.2020.14.4.412.

Circulating microRNA expression profiling in young obese Korean women

• Choi WH
• Ahn J
• Um MY
• Jung CH
• Jung SE
• Ha TY

• KMID: 2504756
• DOI: http://doi.org/10.4162/nrp.2020.14.4.412

Abstract

BACKGROUND/OBJECTIVES
This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20–30 years old) in Korea.
SUBJECTS/METHODS
We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/m²) and 15 obese (BMI > 25 kg/m²) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery.
RESULTS
The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324- 3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = −0.5484, P = 0.0056; miR-378, r = −0.5538, P = 0.0050) and visceral fat content (miR-484, r = −0.6141, P = 0.0014; miR-378, r = −0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism.
CONCLUSION
Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.

Keyword

obesity; microRNAs; gene ontology; humans

Figure

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  Fig. 1 Heatmap of the expressions of miRNAs in obese subjects. The miRNAs are clustered based on the relative expression patterns to lean subjects, with green representing a relatively decreased and red as a relatively increased expression [123].miRNA, microRNA.

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  Fig. 2 Expression of circulating miRNAs in lean and obese subjects. Data are expressed as means ± SEM. The expression levels of miRNAs were normalized to U6 snRNA.miRNA, microRNA; SEM, standard error of mean; snRNA, small nuclear RNA.*P < 0.05, **P < 0.01 and ***P < 0.0001 for the difference between lean and obese subjects.

Reference

1. Ortega FJ, Mercader JM, Catalán V, Moreno-Navarrete JM, Pueyo N, Sabater M, Gómez-Ambrosi J, Anglada R, Fernández-Formoso JA, Ricart W, Frühbeck G, Fernández-Real JM. Targeting the circulating microRNA signature of obesity. Clin Chem. 2013; 59:781–792. PMID: 23396142.

2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116:281–297. PMID: 14744438.

3. Nouraee N, Mowla SJ, Calin GA. Tracking miRNAs' footprints in tumor-microenvironment interactions: insights and implications for targeted cancer therapy. Genes Chromosomes Cancer. 2015; 54:335–352. PMID: 25832733.

4. Nolte-'t Hoen EN, Van Rooij E, Bushell M, Zhang CY, Dashwood RH, James WP, Harris C, Baltimore D. The role of microRNA in nutritional control. J Intern Med. 2015; 278:99–109. PMID: 25832550.

5. Presnell SR, Al-Attar A, Cichocki F, Miller JS, Lutz CT. Human natural killer cell microRNA: differential expression of MIR181A1B1 and MIR181A2B2 genes encoding identical mature microRNAs. Genes Immun. 2015; 16:89–98. PMID: 25410655.

6. Qiu ZL, Shen CT, Song HJ, Wei WJ, Luo QY. Differential expression profiling of circulation microRNAs in PTC patients with non-131I and 131I-avid lungs metastases: a pilot study. Nucl Med Biol. 2015; 42:499–504. PMID: 25682061.

7. Tsochandaridis M, Nasca L, Toga C, Levy-Mozziconacci A. Circulating microRNAs as clinical biomarkers in the predictions of pregnancy complications. BioMed Res Int. 2015; 2015:294954. PMID: 25699269.

8. Keller A, Leidinger P, Bauer A, Elsharawy A, Haas J, Backes C, Wendschlag A, Giese N, Tjaden C, Ott K, Werner J, Hackert T, Ruprecht K, Huwer H, Huebers J, Jacobs G, Rosenstiel P, Dommisch H, Schaefer A, Müller-Quernheim J, Wullich B, Keck B, Graf N, Reichrath J, Vogel B, Nebel A, Jager SU, Staehler P, Amarantos I, Boisguerin V, Staehler C, Beier M, Scheffler M, Büchler MW, Wischhusen J, Haeusler SF, Dietl J, Hofmann S, Lenhof HP, Schreiber S, Katus HA, Rottbauer W, Meder B, Hoheisel JD, Franke A, Meese E. Toward the blood-borne miRNome of human diseases. Nat Methods. 2011; 8:841–843. PMID: 21892151.

9. Papadopoulos EI, Yousef GM, Scorilas A. Gemcitabine impacts differentially on bladder and kidney cancer cells: distinct modulations in the expression patterns of apoptosis-related microRNAs and BCL2 family genes. Tumour Biol. 2015; 36:3197–3207. PMID: 25833690.

10. Lorenzen JM. Vascular and circulating microRNAs in renal ischaemia-reperfusion injury. J Physiol. 2015; 593:1777–1784. PMID: 25691473.

11. Russo F, Di Bella S, Nigita G, Macca V, Laganà A, Giugno R, Pulvirenti A, Ferro A. miRandola: extracellular circulating microRNAs database. PLoS One. 2012; 7:e47786. PMID: 23094086.

12. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008; 105:10513–10518. PMID: 18663219.

13. Seeger T, Fischer A, Muhly-Reinholz M, Zeiher AM, Dimmeler S. Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice. Obesity (Silver Spring). 2014; 22:2352–2360. PMID: 25141837.

14. Yeh CL, Cheng IC, Hou YC, Wang W, Yeh SL. MicroRNA-125a-3p expression in abdominal adipose tissues is associated with insulin signalling gene expressions in morbid obesity: observations in Taiwanese. Asia Pac J Clin Nutr. 2014; 23:331–337. PMID: 24901105.

15. Oger F, Gheeraert C, Mogilenko D, Benomar Y, Molendi-Coste O, Bouchaert E, Caron S, Dombrowicz D, Pattou F, Duez H, Eeckhoute J, Staels B, Lefebvre P. Cell-specific dysregulation of microRNA expression in obese white adipose tissue. J Clin Endocrinol Metab. 2014; 99:2821–2833. PMID: 24758184.

16. Wang R, Hong J, Cao Y, Shi J, Gu W, Ning G, Zhang Y, Wang W. Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults. Eur J Endocrinol. 2015; 172:291–300. PMID: 25515554.

17. Kilic ID, Dodurga Y, Uludag B, Alihanoglu YI, Yildiz BS, Enli Y, Secme M, Bostancı HE. MicroRNA -143 and -223 in obesity. Gene. 2015; 560:140–142. PMID: 25637573.

18. Heneghan HM, Miller N, McAnena OJ, O'Brien T, Kerin MJ. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab. 2011; 96:E846–50. PMID: 21367929.

19. Arner P, Kulyté A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol. 2015; 11:276–288. PMID: 25732520.

20. Klöting N, Berthold S, Kovacs P, Schön MR, Fasshauer M, Ruschke K, Stumvoll M, Blüher M. MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One. 2009; 4:e4699. PMID: 19259271.

21. Mentzel CM, Anthon C, Jacobsen MJ, Karlskov-Mortensen P, Bruun CS, Jørgensen CB, Gorodkin J, Cirera S, Fredholm M. Gender and obesity specific microRNA expression in adipose tissue from lean and obese pigs. PLoS One. 2015; 10:e0131650. PMID: 26222688.

22. Oh SW, Shin SA, Yun YH, Yoo T, Huh BY. Cut-off point of BMI and obesity-related comorbidities and mortality in middle-aged Koreans. Obes Res. 2004; 12:2031–2040. PMID: 15687405.

23. Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG, Roayaei J, Stephens R, Baseler MW, Lane HC, Lempicki RA. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007; 8:R183. PMID: 17784955.

24. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11:85–97. PMID: 21252989.

25. Iacomino G, Siani A. Role of microRNAs in obesity and obesity-related diseases. Genes Nutr. 2017; 12:23. PMID: 28974990.

26. Quinet EM, Savio DA, Halpern AR, Chen L, Schuster GU, Gustafsson JA, Basso MD, Nambi P. Liver X receptor (LXR)-beta regulation in LXRalpha-deficient mice: implications for therapeutic targeting. Mol Pharmacol. 2006; 70:1340–1349. PMID: 16825483.

27. Tang X, Muniappan L, Tang G, Ozcan S. Identification of glucose-regulated miRNAs from pancreatic beta cells reveals a role for miR-30d in insulin transcription. RNA. 2009; 15:287–293. PMID: 19096044.

28. Wang K, Long B, Jiao JQ, Wang JX, Liu JP, Li Q, Li PF. MiR-484 regulates mitochondrial network through targeting Fis1. Nat Commun. 2012; 3:781. PMID: 22510686.

29. Yoon Y, Galloway CA, Jhun BS, Yu T. Mitochondrial dynamics in diabetes. Antioxid Redox Signal. 2011; 14:439–457. PMID: 20518704.