Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2017; 23(30): 5508-5518
Published online Aug 14, 2017. doi: 10.3748/wjg.v23.i30.5508
MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett’s esophagus
Loveena Sreedharan, George C Mayne, David I Watson, Timothy Bright, Reginald V Lord, Alfiya Ansar, Tingting Wang, Jakob Kist, David StJ Astill, Damian J Hussey
Loveena Sreedharan, George C Mayne, David I Watson, Timothy Bright, Alfiya Ansar, Tingting Wang, Jakob Kist, Damian J Hussey, Department of Surgery, Flinders Medical Centre, Flinders University, Adelaide, SA 5042, Australia
Reginald V Lord, St Vincent’s Centre for Applied Medical Research, Sydney, NSW 2011, Australia
David StJ Astill, Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, SA 5042, Australia
Author contributions: Watson DI, Bright T, Lord RV and Hussey DJ designed and coordinated the research; Watson DI, Lord RV and Hussey DJ obtained the funding that supported this research; Watson DI and Bright T collected patient samples; Sreedharan L, Ansar A, Wang T and Kist J prepared the tissue samples and performed the molecular studies; Sreedharan L, Mayne GC and Hussey DJ analyzed the data; Astill DS performed the histopathology; Sreedharan L, Mayne GC and Hussey DJ wrote the first draft of the paper; all authors contributed to revision of the manuscript in its final version.
Supported by National Health and Medical Research Council, Australia, No. APP1008337.
Institutional review board statement: This study was reviewed and approved by the Southern Adelaide Clinical Human Research Ethics Committee.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: Datasets have been made available on the Gene Expression Omnibus (GEO) website, Accession number GSE94854. The data can be downloaded from https://www.ncbi.nlm.nih.gov/geo/info/download.html.
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: Damian J Hussey, PhD, Department of Surgery, Flinders Medical Centre, Flinders University, Bedford Park, Adelaide, SA 5042, Australia. damian.hussey@flinders.edu.au
Telephone: +61-8-82046091 Fax: +61-8-82046130
Received: February 27, 2017
Peer-review started: February 28, 2017
First decision: April 16, 2017
Revised: May 18, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: August 14, 2017
Processing time: 167 Days and 13.3 Hours
Abstract
AIM

To investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett’s esophagus.

METHODS

High throughput screening using TaqMan® Array Human MicroRNA quantitative PCR was used to determine expression levels of 754 microRNAs in distal esophageal mucosa (1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett’s esophagus using argon plasma coagulation vs pretreatment mucosa, post-treatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett’s esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted mRNA target pathway analysis was used to investigate the functional involvement of differentially expressed microRNAs.

RESULTS

Forty-four microRNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen microRNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine microRNAs (miR-424-5p, miR-127-3p, miR-98-5p, miR-187-3p, miR-495-3p, miR-34c-5p, miR-223-5p, miR-539-5p, miR-376a-3p, miR-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These microRNAs were also more highly expressed in Barrett’s esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in the regulation of cell survival signalling pathways. Three microRNAs (miR-187-3p, miR-135b-5p and miR-31-5p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These miRNAs were expressed at similar levels in pre-ablation Barrett’s esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in regulating the expression of proteins that contribute to barrier function.

CONCLUSION

Neosquamous mucosa arising after ablation of Barrett’s esophagus expresses microRNAs that may contribute to decreased barrier function and microRNAs that may be involved in the regulation of survival signaling pathways.

Keywords: Neosquamous; Barrett’s esophagus; Ablation

Core tip: We report that the microRNA profile of esophageal neosquamous mucosa developing after ablation of Barrett’s esophagus is different to normal squamous epithelium, and that the differentially expressed microRNAs in neosquamous mucosa may regulate survival signalling pathways and contribute to decreased barrier function in the esophagus.