MicroRNAs in esophageal cancer

Esophageal cancer (EC) is the sixth leading cause of cancer death worldwide. More than 90% of ECs are either esophageal squamous cell carcinomas (ESCC) or adenocarcinomas (EAC). These two histological subtypes share certain risk factors and pathogenic pathways, but mostly have distinct etiology and pathogenesis. The development of EAC generally follows the metaplasia-dysplasia- carcinoma sequence and Barrett's esophagus (BE) is a precursor of EAC. MicroRNAs (miRNAs) are small non-coding RNAs that bind to the 3^′ untranslated region of target mRNA and post-Transcriptionally regulates gene expression. Several miRNA profiling and candidate miRNA studies have identified changes in miRNA expression that take place during the pathogenesis and progression of EC. MiR-21 is up-regulated in both ESCC and EAC, whereas a number of other miRNAs are distinctly dysregulated in ESCC or EAC. MiRNA expression profiles can distinguish between BE and EAC. The miR-106b-25 polycistron is up-regulated progressively at successive stages of BE and EAC. MiR-196a is up-regulated in high-grade dysplasia and EAC, and is a potential biomarker of progression from BE to EAC. A few mRNA targets of select miRNAs, including miR-21, miR-196a, miR-10b, miR-145, miR-133a, miR-133b, and miR-106b-25, have been identified and validated in EC. Several studies have shown the prognostic values of selected miRNAs. Finally, germline genetic variations affecting the binding of miRNA and mRNA have been found to be associated with the risk of EC. A better understanding of the miRNA expression in EC may provide new avenues for the diagnosis, prognosis, and therapy of this deadly disease.