Barrett’s oesophagus is the only identifiable precursor to oesophageal adenocarcinoma. Gastroesophageal reflux-induced inflammation in Barrett’s oesophagus mucosa stimulates cancer-promoting processes including cellular proliferation and apoptosis resistance. Medical or surgical therapies are used to treat reflux and might minimise the risk of Barrett’s oesophagus cancer progression. These therapies differ in effectiveness of control of acid and bile reflux, and might impact differently on expression of inflammatory molecules. MicroRNAs regulate gene expression to influence biological processes including inflammation, proliferation and apoptosis.
We used microarray discovery, relative quantitative reverse-transcriptase polymerase chain reaction, and Western blotting to evaluate the expression of microRNAs and their mRNA targets (or downstream effectors of their mRNA targets) in Barrett’s oesophagus mucosa from patients undergoing medical (n=17) vs surgical (n=19) treatment of reflux.
The expression of let-7a, let-7f, miR-98 and miR-26a was higher in the surgical group (p<0.05). KRAS and E2F2 gene transcripts (let-7 targets that promote proliferation) were expressed at lower levels in the surgical group (p<0.05). The expression of MCL1 gene transcript, which is induced by phosphorylated STAT3 (a downstream effector of the let-7 target gene transcript IL6) to promote apoptosis resistance, was lower in the surgical group (p<0.05). Overall, we observed higher levels of let-7 microRNAs and correspondingly lower levels of their target gene transcripts (or downstream effectors) in the surgical group compared to the medical group.
Let-7 microRNAs are widely reported for their role in mediating inflammatory processes and our data is consistent with lower levels of reflux-induced inflammation, and correspondingly lower levels of pro-proliferative and anti-apoptotic gene expression in the surgical group. These results might have implications on the choice of reflux therapy vs. long-term cancer risk.