Many studies on the therapeutic potential of such microRNA engineering have shown promising results. For instance, intratumoral as well as systemic delivery of synthetic let-7 microRNA, whose level is downregulated in lung cancer, was found to cause tumor regression in a mouse model of lung

cancer (68), and disease progression in a mouse model of hepatocellular carcinoma was found to be halted by systemic delivery of adeno-associated viruses engineered to express miR-26a (69). MicroRNAs and esophageal carcinoma Guo and colleagues were the first to report microRNA expression profiles in esophageal cancer, in 2008. Microarrays were used to profile 435 microRNAs in RNA extracted Inhibitors,research,lifescience,medical from fresh-frozen specimens of 31 pairs of ESCC and corresponding

adjacent normal esophageal tissues (70). One-hundred-ninety-one microRNAs were considered Inhibitors,research,lifescience,medical detectable, and their expression profiles could be used to discern Dabrafenib clinical trial cancerous from normal tissue with >90% accuracy. MicroRNAs miR-25, miR-424 and miR-151 showed upregulation, and miR-100, miR-99a, miR-29c, and miR-140* showed reduction in cancerous Inhibitors,research,lifescience,medical tissue. Higher expression of miR-103 and miR-107, known to affect metastatic potential of cancers by downregulating Dicer levels (58), was associated with poor prognosis. In a study that was published in the same year, Feber, et al., used RNA from fresh-frozen tissue samples from ten cases each of EAC and ESCC, and five cases of BE, to assay the expression of 328 human microRNAs (71). Compared to normal esophagus, miR-203 and miR-205 were expressed two-to-ten-fold less in all three diseases, whereas miR-21 levels were three-to-five-fold Inhibitors,research,lifescience,medical higher. Reduced levels of miR-203 and

miR-205 were also observed in columnar epithelium compared to normal squamous epithelium in a study that examined 377 microRNAs in 16 individuals using microarrays (72). Levels of miR-205 were also found to be lower in BE mucosa compared to normal adjacent epithelium as well as to neosquamous epitheium generated following ablation of Barrett’s epithelium with Argon plasma coagulation in a study involving nine patients (73). MicroRNA miR-21 was Inhibitors,research,lifescience,medical also identified as overexpressed in a study that used RT-PCR to examine 20 cases of ESCC and seven ESCC cell-lines, and in two other studies, and it has been shown to be PDK4 an oncogene that promoted cell transformation by targeting transcripts for the Programmed cell death 4 (PDCD4) protein (72), (74)-(76). Though some microRNAs, such as miR-21, miR-100, miR-203 and miR-205, were identified as being affected in esophageal carcinoma in more than one of the aforementioned studies, many, like miR-143, miR-145 and miR-215, whose levels are increased in EAC as well as BE (74), were not. Characteristics of patient populations and RNA quantification technologies, and differences in sample-sizes and data analyses are believed to be responsible for this, a theme that occurs recurrently in such biomarker discovery work.