Analysis of Circular RNAs in the Coronary Arteries of Patients with Kawasaki Disease
0
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Objectives: Kawasaki disease is a disease in children that presents with diverse symptoms including acute fever, conjunctivitis, body rash, swollen lymph nodes of the neck, and peeling of the skin on the hands and feet. Although patients with Kawasaki disease are continually observed and diagnosed, there are no established molecular markers to diagnose this disease quickly and accurately. Moreover, there have been very few studies on the molecular mechanism underlying Kawasaki disease. Methods: The expression profiles of circular RNAs (circRNAs) from coronary artery tissue of patients with Kawasaki disease were analyzed using public sequencing datasets. After selecting reliable sequencing libraries and high-quality reads, bioinformatics pipelines were applied to quantify the expression of back-splicing reads of host genes. Results: Many circRNAs were identified to be differentially expressed between the controls and patients with Kawasaki disease. Among them, circRNAs originating from host genes including homeodomain interacting protein kinase 3 (circHIPK3), zinc finger protein 124 (circZNF124), WAS protein homolog associated with actin, Golgi membranes, and microtubules pseudogene 1 (circWHAMMP1), SLAIN motif family, member 2 (circSLAIN2), and ataxia telangiectasia mutated (circATM) were down-regulated significantly in untreated patients with Kawasaki disease. Importantly, the level of these circRNAs returned to normal in the coronary arteries of treated patients, suggesting these circRNAs are possible molecular markers for Kawasaki disease. For circWHAMMP1 and circZNF124, the microRNAs that may be regulated by these circRNAs were also identified. Conclusions: This study will contribute to future research seeking to determine the regulatory pathways involved in the pathogenesis of Kawasaki disease.
Abstract
Objectives: Kawasaki disease is a disease in children that presents with diverse symptoms including acute fever, conjunctivitis, body rash, swollen lymph nodes of the neck, and peeling of the skin on the hands and feet. Although patients with Kawasaki disease are continually observed and diagnosed, there are no established molecular markers to diagnose this disease quickly and accurately. Moreover, there have been very few studies on the molecular mechanism underlying Kawasaki disease. Methods: The expression profiles of circular RNAs (circRNAs) from coronary artery tissue of patients with Kawasaki disease were analyzed using public sequencing datasets. After selecting reliable sequencing libraries and high-quality reads, bioinformatics pipelines were applied to quantify the expression of back-splicing reads of host genes. Results: Many circRNAs were identified to be differentially expressed between the controls and patients with Kawasaki disease. Among them, circRNAs originating from host genes including homeodomain interacting protein kinase 3 (circHIPK3), zinc finger protein 124 (circZNF124), WAS protein homolog associated with actin, Golgi membranes, and microtubules pseudogene 1 (circWHAMMP1), SLAIN motif family, member 2 (circSLAIN2), and ataxia telangiectasia mutated (circATM) were down-regulated significantly in untreated patients with Kawasaki disease. Importantly, the level of these circRNAs returned to normal in the coronary arteries of treated patients, suggesting these circRNAs are possible molecular markers for Kawasaki disease. For circWHAMMP1 and circZNF124, the microRNAs that may be regulated by these circRNAs were also identified. Conclusions: This study will contribute to future research seeking to determine the regulatory pathways involved in the pathogenesis of Kawasaki disease.
참고문헌 (26)
- Newburger JW, "Kawasaki disease", J Am Coll Cardiol, 67, pp.1738~1749 (2016)
- Cohen E, "Kawasaki disease at 50 years", JAMA Pediatr, 170, pp.1093~1099 (2016)
- Uehara R, "Epidemiology of Kawasaki disease in Asia, Europe, and the United States", J Epidemiol, 22, pp.79~85 (2012)
- 하상미, "Epidemiologic Study on Kawasaki Disease in Korea, 2007-2014: Based on Health Insurance Review & Assessment Service Claims", Journal of Korean Medical Science, 31(9), pp.1445~1449 (2016), 대한의학회
- Newburger JW, "Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association", Circulation, 110, pp.2747~2771 (2004)
- Glažar P, "circBase: a database for circular RNAs", RNA, 20, pp.1666~1670 (2014)
- Ebbesen KK, "Circular RNAs: identification, biogenesis and function", Biochim Biophys Acta, 1859, pp.163~168 (2016)
- Wilusz JE, "Circular RNAs: unexpected outputs of many protein-coding genes", RNA Biol, 14, pp.1007~1017 (2017)
- Kulcheski FR, "Circular RNAs are miRNA sponges and can be used as a new class of biomarker", J Biotechnol, 238, pp.42~51 (2016)
- Du WW, "Identifying and characterizing circRNA-protein interaction", Theranostics, 7, pp.4183~4191 (2017)
- Pamudurti NR, "Translation of CircRNAs", Mol Cell, 66, pp.9~21.e7 (2017)
- Legnini I, "Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis", Mol Cell, 66, pp.22~37.e9 (2017)
- Rowley AH, "The transcriptional profile of coronary arteritis in Kawasaki disease", BMC Genomics, 16, pp.1076~ (2015)
- Bolger AM, "Trimmomatic: a flexible trimmer for Illumina sequence data", Bioinformatics, 30, pp.2114~2120 (2014)
- Dobin A, "STAR: ultrafast universal RNA-seq aligner", Bioinformatics, 29, pp.15~21 (2013)
- Cheng J, "Specific identification and quantification of circular RNAs from sequencing data", Bioinformatics, 32, pp.1094~1096 (2016)
- Tyner C, "The UCSC Genome Browser database: 2017 update", Nucleic Acids Res, 45, pp.D626~D634 (2017)
- Rowley AH, "A study of cardiovascular miRNA biomarkers for Kawasaki disease", Pediatr Infect Dis J, 33, pp.1296~1299 (2014)
- Agarwal V, "Predicting effective microRNA target sites in mammalian mRNAs", eLife, 4, pp.e05005~ (2015)
- Memczak S, "Circular RNAs are a large class of animal RNAs with regulatory potency", Nature, 495, pp.333~338 (2013)
- Hansen TB, "Natural RNA circles function as efficient microRNA sponges", Nature, 495, pp.384~388 (2013)
- Clough E, "The gene expression omnibus database", Methods Mol Biol, 1418, pp.93~110 (2016)
- Shan K, "Circular noncoding RNA HIPK3 mediates retinal vascular dysfunction in diabetes mellitus", Circulation, 136, pp.1629~1642 (2017)
- Zheng Q, "Circular RNA profiling reveals an abundant circHIPK3that regulates cell growth by sponging multiple miRNAs", Nat Commun, 7, pp.11215~ (2016)
- Liang S, "miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2", Exp Ther Med, 14, pp.1095~1103 (2017)
- Hori D, "miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling", PLoS One, 12, pp.e0174108~ (2017)