Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2019; 25(41): 6273-6288
Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6273
Increased circulating circular RNA_103516 is a novel biomarker for inflammatory bowel disease in adult patients
Yu-Lan Ye, Juan Yin, Tong Hu, Li-Ping Zhang, Long-Yun Wu, Zhi Pang
Yu-Lan Ye, Juan Yin, Tong Hu, Li-Ping Zhang, Long-Yun Wu, Zhi Pang, Department of Gastroenterology, the North District of the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215008, Jiangsu Province, China
Author contributions: Ye YL and Pang Z contributed to study conception and design; Ye YL contributed to data acquisition, analysis, and interpretation and writing of the article; Yin J, Hu T, Zhang LP, Wu LY, and Pang Z contributed to the editing and review of the article. All authors read and approved the final manuscript.
Supported by the Natural Science Foundation of Jiangsu Province, No. BK20161232; and the Suzhou Special Project of Diagnosis and Treatment for Key Clinical Disease, No. LCZX201715.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Affiliated Suzhou Hospital of Nanjing Medical University.
Informed consent statement: All participants signed an informed consent form prior to study enrolment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
STROBE statement: The guidelines of the STROBE Statement were adopted for this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi Pang, MD, Chief Doctor, Full Professor, Department of Gastroenterology, the North District of the Affiliated Suzhou Hospital of Nanjing Medical University, No. 242, Guangji Road, Suzhou 215008, Jiangsu Province, China. pangzhi0273@sina.com
Telephone: +86-512-62363008 Fax: +86-512-62362502
Received: August 19, 2019
Peer-review started: August 19, 2019
First decision: September 10, 2019
Revised: September 23, 2019
Accepted: October 17, 2019
Article in press: October 17, 2019
Published online: November 7, 2019
Processing time: 79 Days and 22.6 Hours
Abstract
BACKGROUND

Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level, circular RNAs (circRNAs) participate in the pathogenesis of a variety of diseases and are considered ideal biomarkers of human disease.

AIM

To examine the expression of circRNA_103516 in inflammatory bowel disease (IBD) and its associations with clinical phenotypes and inflammatory cytokines.

METHODS

Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IBD, healthy controls (HCs), and patient controls (PCs). Expression of circRNA_103516 and hsa-miR-19b-1-5p was assessed by quantitative reverse transcription-polymerase chain reaction. Crohn's disease activity index (CDAI), Mayo score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were measured. To assess the inflammatory cytokines tumour necrosis factor α (TNF-α), interferon-γ (IFN-γ), and interleukin-10 (IL-10), blood samples were analysed by flow cytometry.

RESULTS

Ninety Crohn’s disease (CD) and 90 ulcerative colitis (UC) patients, 80 HCs, and 35 PCs were included in the study. CircRNA_103516 was upregulated in CD and UC patients compared with HCs and PCs (P < 0.05). The area under the curve of circRNA_103516 for diagnosing CD and UC was 0.790 and 0.687, respectively. In addition, circRNA_103516 levels were increased in active CD and UC compared with remittent groups (P = 0.027, P = 0.045). Furthermore, in CD, circRNA_103516 correlated positively with CDAI (P < 0.001), CRP (P < 0.001), ESR (P < 0.001), TNF­α (P < 0.001), and IFN-γ (P < 0.001) and negatively correlated with IL-10 (P = 0.006). In UC patients, circRNA_103516 correlated with Mayo score (P < 0.001), CRP (P < 0.001), ESR (P < 0.001), TNF­α (P < 0.001), IFN-γ (P =0.011), and IL-10 (P = 0.002). Additionally, circRNA_103516 correlated positively with stricturing (P = 0.018) and penetrating (P = 0.031) behaviour. Moreover, hsa-miR-19b-1-5p correlated negatively with circRNA_103516 in CD.

CONCLUSION

CircRNA_103516 levels in PBMCs can be considered an ideal candidate biomarker for diagnosing IBD. Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.

Keywords: Circular RNA; Circular RNA_103516; Inflammatory bowel diseases; Biomarker

Core tip: The study aimed to assess circular RNA (circRNA)_103516 in peripheral blood mononuclear cells of inflammatory bowel disease (IBD) patients and evaluate its potential as a biomarker in Crohn’s disease and ulcerative colitis patients with regard to clinical phenotype and inflammatory cytokines. Our results showed that PBMC circRNA_103516 levels may be considered an ideal candidate biomarker for the diagnosis of IBD and have the ability to predict clinical outcomes in IBD. Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.