ORIGINAL ARTICLES Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus HONGLEI WANG, WUJIAN PENG, XIN OUYANG, WUXIAN LI, and YONG DAI GUANGDONG, P. R. CHINA Aberrant expression of microRNAs (miRNAs) has been identified in various diseases. Recent studies demonstrated that miRNAs can be detected in the circulation and serve as potential biomarkers of various diseases. Moreover, the detection of circu- lating miRNAs can provide important novel information concerning diseases. In this study, a miRNA profile was used to determine the aberrantly expressed circulating miRNAs in patients with systemic lupus erythematosus (SLE) compared with patients with rheumatoid arthritis (RA) and healthy controls (HCs). To further confirm the micro- array data, we identified 8 miRNAs (miR-126, miR-21, miR-451, miR-223, miR-16, miR- 125a-3p, miR-155, and miR-146a) by real-time quantitative PCR (qRT-PCR) in 20 healthy controls and in 55 patients, of whom 30 patients were diagnosed with SLE and 25 were diagnosed with RA. Consistent with the microarray data, miR-126 was specifically enriched only in the blood of the SLE patients, but 4 other miRNAs (miR- 21, miR-451, miR-223, and miR-16) were upregulated in the patients with SLE and were also significantly increased in the patients with RA. In contrast, miR-125a-3p, miR-155, and miR-146a showed a trend toward significantly reduced levels in the pa- tients with SLE. In addition, to further estimate the potential roles of these differentially expressed circulating miRNAs in the pathogenesis of SLE, we used a bioinformatics exploratory analysis and identified a number of significantly enriched pathways, which implied that most dysregulated circulating miRNAs might be involved in vari- ous signal transduction pathways and cell interactions, particularly the mitogen- activated protein kinase signaling pathway. Based on these findings, we postulate that aberrantly expressed plasma miRNAs could be attractive as candidates for putative biomarkers of SLE and may help elucidate the possible pathogenesis of SLE. (Translational Research 2012;160:198–206) Abbreviations: DMARDs ¼ disease-modifying antirheumatic drugs; DNMT1 ¼ DNA methyltrans- ferase 1; ERK pathway signaling ¼ extracellular signal-regulated kinase pathway signaling; HCs ¼ healthy controls; IFN ¼ interferon; IRF-5 ¼ IFN regulatory factor 5; KLF13 ¼ Kruppel-like factor 13; miRNA ¼ microRNA; mRNA ¼ messenger RNA; MAPK ¼ mitogen-activated protein kinase; OA ¼ osteoarthritis; PBMC ¼ peripheral blood mononuclear cells; PKC ¼ protein kinase C; qRT-PCR ¼ real-time quantitative polymerase chain reaction; RA ¼ rheumatoid arthritis; SLE ¼ systemic lupus erythematosus; TLR ¼ Toll-like receptors From the Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, Guangdong, P. R. China. Conflict of interest: None. Supported by a grant from the National Natural Science Foundation of the P.R. China (No: 30972741). Submitted for publication December 26, 2011; revision submitted April 1, 2012; accepted for publication April 5, 2012. Reprint requests: Yong Dai, MD, PhD, Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People 0 s Hospital), Jinan University, Shenzhen, Guangdong, 518020, P. R. China; e-mail: daiyong22@yahoo.com.cn. 1931-5244/$ - see front matter Ó 2012 Mosby, Inc. All rights reserved. doi:10.1016/j.trsl.2012.04.002 198