Flexible and Versatile as a Chameleon—Sophisticated Functions of microRNA-199a

Although widely studied in the past decade, our knowledge of the functional role of microRNAs (miRNAs) remains limited. Among the many miRNAs identified in humans, we focus on miR-199a due to its varied and important functions in diverse models and systems. Its expression is finely regulated by promoter methylation and direct binding of transcription factors such as TWIST1. During tumorigenesis, depending on the nature of the cancer, miR-199a, especially its -3p mature form, may act as either a potential tumor suppressor or an oncogene. Its 5p mature form has been shown to protect cardiomyocytes from hypoxic damage via its action on HIF1α. It also has a functional role in stem cell differentiation, embryo development, hepatitis, liver fibrosis, etc. Though it has varied biological activities, its regulation has not been reviewed. The varied and protean functions of miR-199a suggest that efforts to generalize the action of a miRNA are problematic. This review provides a comprehensive survey of the literature on miR-199a as an example of the complexity of miRNA biology and suggests future directions for miRNA research.