Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2016; 22(19): 4716-4731
Published online May 21, 2016. doi: 10.3748/wjg.v22.i19.4716
Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn’s disease
Dong Chen, Jiang Liu, Hui-Ying Zhao, Yi-Peng Chen, Zun Xiang, Xi Jin
Dong Chen, Hui-Ying Zhao, Department of Colorectal Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Jiang Liu, Department of Gastroenterology, Huzhou Central Hospital, Huzhou 310003, Zhejiang Province, China
Yi-Peng Chen, Zun Xiang, Xi Jin, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Chen D and Liu J performed the majority of experiments; Zhao HY, Chen YP and Xiang Z participated in clinical sample collection, microarray, qRT-PCR and data analysis; Jin X designed the study and wrote the manuscript; Liu J and Jin X contribute equally as the first author.
Supported by National Natural Science Foundation of China, No. 81370008 and No. 81000169; Natural Science Foundation of Zhejiang Province, No. R2110159, No. LY15H030006 and No. LY16H030003; and Science Technology Project of Zhejiang Province, No. 2014C33205.
Institutional review board statement: This study was approved by the institution review board of the First Affiliated Hospital of Zhejiang University and conducted in accordance with the Declaration of Helsinki.
Conflict-of-interest statement: There are no conflicts of interest or commercial financial support for this manuscript.
Data sharing statement: No additional data are available.
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/
Correspondence to: Xi Jin, PhD, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. jxfl007@zju.edu.cn
Telephone: +86-571-87236611 Fax: +86-571-87236611
Received: February 11, 2016
Peer-review started: February 13, 2016
First decision: March 7, 2016
Revised: March 10, 2016
Accepted: March 30, 2016
Article in press: March 30, 2016
Published online: May 21, 2016
Abstract

AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn’s disease (CD) patients.

METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.

RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 (NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.

CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.

Keywords: Crohn’s disease, Long noncoding RNA, Inflammatory bowel disease, Plasma, Microarray

Core tip: The pathogenesis of Chrohn’s disease (CD) is unclear while increasing evidence supports the involvement of epigenomic regulation. In this study, we jointly used microarray screening and qRT-PCR verification to achieve the plasma specific long noncoding RNAs expression profile of patients with CD and their potential regulation of downstream mRNAs. Our results would provide preliminary data for non-invasive diagnosis of CD and a reservoir for specific lncRNA-mRNA pathway exploration in the future.