MicroRNA Dysregulations in Gastrointestinal Cancers: Pathophysiological and Clinical Perspectives

ABSTRACT

Two common gastrointestinal cancers, namely, gastric and colorectal cancers, cause high mortality and morbidity. The development of gastrointestinal cancers usually follows stepwise processes with recognizable pre-neoplastic changes. A class of noncoding RNA known as microRNA (miRNA) is increasingly recognized to play pleiotropic functions in the multistep development of gastrointestinal cancers. Abnormal patterns of miRNA expression in gastric and colorectal cancers have been widely reported. These dysregulated miRNAs function as novel proto-oncogenes and tumor-suppressor genes by controlling cellular malignant phenotypes, including unchecked cell proliferation, resistance to apoptosis, enhanced invasiveness and metastasis, and angiogenesis. Moreover, certain polymorphisms in miRNA genes or miRNA-binding sites are associated with disease risks whereas detection of circulating or fecal miRNAs may facilitate early diagnosis. The prognostic functions of a number of dysregulated miRNAs in gastrointestinal cancers have also been established. Delineating the pathophysiological basis of miRNA dysregulation will further our understanding of the pathogenesis of these two potentially fatal diseases. Such efforts will also result in the development of miRNA-based biomarkers and therapeutics for the risk stratification, diagnosis, prognostication, and treatment of gastrointestinal cancers.