摘要
To investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett’s esophagus. METHODSHigh throughput screening using TaqMan<sup>®</sup> 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. RESULTSForty-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. CONCLUSIONNeosquamous 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.
AIM To investigate the micro RNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett's esophagus.METHODS High throughput screening using Taq Man~ Array Human Micro RNA quantitative PCR was used to determine expression levels of 754 micro RNAs 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, posttreatment 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 m RNA target pathway analysis was used to investigate the functional involvement of differentially expressed micro RNAs.RESULTS Forty-four micro RNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen micro RNAs 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 micro RNAs(mi R-424-5p, mi R-127-3p, mi R-98-5p, mi R-187-3p, mi R-495-3p, mi R-34c-5p, mi R-223-5p, mi R-539-5p, mi R-376a-3p, mi R-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These micro RNAs 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 micro RNAs may be involved in the regulation of cell survival signalling pathways. Three micro RNAs(mi R-187-3p, mi R-135b-5p and mi R-31-5p) were expressed at higher levels in postablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These mi RNAs were expressed at similar levels in preablation Barrett's esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these micro RNAs 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 micro RNAs that may contribute to decreased barrier function and micro RNAs that may be involved in the regulation of survival signaling pathways.
基金
Supported by National Health and Medical Research Council,Australia,No.APP1008337