Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.

[1]  Y. Long,et al.  Circular RNA in blood corpuscles combined with plasma protein factor for early prediction of pre‐eclampsia , 2016, BJOG : an international journal of obstetrics and gynaecology.

[2]  Zhengcai Liu,et al.  Circular RNA Expression Profile of Pancreatic Ductal Adenocarcinoma Revealed by Microarray , 2016, Cellular Physiology and Biochemistry.

[3]  Can Rui,et al.  Potential Significance of Circular RNA in Human Placental Tissue for Patients with Preeclampsia , 2016, Cellular Physiology and Biochemistry.

[4]  Junxia Chen,et al.  Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma , 2016, Scientific Reports.

[5]  W. Niu,et al.  hsa_circRNA_103636: potential novel diagnostic and therapeutic biomarker in Major depressive disorder. , 2016, Biomarkers in medicine.

[6]  Hong-jin Wu,et al.  Microarray Expression Profile of Circular RNAs in Heart Tissue of Mice with Myocardial Infarction-Induced Heart Failure , 2016, Cellular Physiology and Biochemistry.

[7]  Chuanxin Wang,et al.  Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development , 2016, Medicine.

[8]  H. Xie,et al.  Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer , 2016, Oncotarget.

[9]  B. Chiang,et al.  Lymphocyte-activation gene 3(+) (LAG3(+)) forkhead box protein 3(-) (FOXP3(-)) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis. , 2016, Journal of autoimmunity.

[10]  Haimin Li,et al.  Circular RNA: A new star of noncoding RNAs. , 2015, Cancer letters.

[11]  L. Laurent,et al.  Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development , 2015, Genome Biology.

[12]  Petar Glažar,et al.  Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. , 2015, Molecular cell.

[13]  Xiaoyan Mo,et al.  Using circular RNA as a novel type of biomarker in the screening of gastric cancer. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[14]  Li Yang,et al.  Regulation of circRNA biogenesis , 2015, RNA biology.

[15]  Dongming Liang,et al.  Short intronic repeat sequences facilitate circular RNA production , 2014, Genes & development.

[16]  N. Sharpless,et al.  Detecting and characterizing circular RNAs , 2014, Nature Biotechnology.

[17]  Walter J. Lukiw,et al.  Circular RNA (circRNA) in Alzheimer's disease (AD) , 2013, Front. Genet..

[18]  Julia Salzman,et al.  Cell-Type Specific Features of Circular RNA Expression , 2013, PLoS genetics.

[19]  T. Mimori,et al.  Comprehensive microRNA Analysis Identifies miR-24 and miR-125a-5p as Plasma Biomarkers for Rheumatoid Arthritis , 2013, PloS one.

[20]  J. Kjems,et al.  Natural RNA circles function as efficient microRNA sponges , 2013, Nature.

[21]  Sebastian D. Mackowiak,et al.  Circular RNAs are a large class of animal RNAs with regulatory potency , 2013, Nature.

[22]  Michael K. Slevin,et al.  Circular RNAs are abundant, conserved, and associated with ALU repeats. , 2013, RNA.

[23]  A. Silman,et al.  Rheumatoid arthritis classifi cation criteria : an American College of Rheumatology / European League Against Rheumatism collaborative initiative , 2010 .

[24]  Peter Goodfellow,et al.  Circular transcripts of the testis-determining gene Sry in adult mouse testis , 1993, Cell.