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
ARTICLE HIGHLIGHTS
Research background

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), comprises chronic gastrointestinal tract inflammatory disorders. Due to the characteristic of repeated recurrence, the disease activity of IBD must be assessed and monitored repeatedly. Accordingly, non-invasive serological biomarkers may constitute an optimal alternative choice for evaluating and screening disease activity in IBD. Increasing evidence demonstrates that circular RNAs (circRNAs) participate in the pathogenesis of a variety of diseases by modulating gene expression at the transcriptional or post-transcriptional level and are considered ideal biomarkers in human disease.

Research motivation

To date, little is known about the relationships between circRNAs and IBD. Our previous research identified 155 upregulated circRNAs and 229 downregulated circRNAs by microarray analysis of peripheral blood mononuclear cells (PBMCs) from CD patients compared with healthy controls (HCs). Moreover, bioinformatics analysis predicted that hsa_circRNA_103516 might participate in the pathogenesis of IBD by sponging hsa-miR-19b-1-5p.

Research objectives

The aim of this study was to identify expression of circRNA_103516 in IBD and its association with clinical phenotypes and inflammatory cytokines.

Research methods

We performed an observational study. PBMCs were obtained from patients with IBD, HCs, and patient controls. 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. Flow cytometry was used to examine blood samples for the measurement of the inflammatory cytokines tumour necrosis factor-α, interferon-γ (IFN-γ), and interleukin-10 (IL-10). Spearman correlation analysis was performed to determine linear correlations for different groups. Receiver operating characteristic curve analysis was used to assess the clinical diagnostic value of candidate circRNAs. Logistic regression analysis was used to identify risk factors.

Research results

CircRNA_103516 was upregulated in CD and UC. Furthermore, circRNA_103516 correlated positively with CDAI, Mayo score, CRP, ESR, TNF­α, and IFN-γ and negatively with IL-10 in IBD. Additionally, circRNA_103516 correlated positively with stricturing and penetrating behaviour. The predicted hsa-miR-19b-1-5p correlated negatively with circRNA_103516 in CD.

Research conclusions

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

Research perspectives

More large prospective multicentre clinical studies need to be performed for a more applicable conclusion. In addition, miRNA-circRNA interactions were conducted by functional analysis and not by experimental verification. It is imperative to further explore their respective molecular mechanisms and genetic changes to achieve better diagnostic and treatment strategies in the future.