Abstract
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.
Highlights
Until the present time, the identification of certain small RNA molecules as microRNAhas been based on its structure/size
As shown in UCSC genome browser, miR-199a-1 located on Chromosome 19 (Chr19) is embedded in the anti-sense strand of intron 15 of Dynamin 2 (DNM2), whereas miR-199a-2 located on Chromosome 1 (Chr1) is embedded in the anti-sense strand of intron 14 of Dynamin 3 (DNM3)
A similar observation on hepatocellular carcinoma (HCC) studies showed that the anti-invasion effect of miR-199a-5p on its direct target DDR1 varied among individuals and cell lines [34]
Summary
The identification of certain small RNA molecules as microRNA (miRNA). Criteria include hairpin precursor structures, phylogenetic conservation in multiple species, and experimental documentation of a small RNA molecule [1]. The well-conserved miR-199a, identified by diverse high-throughput screenings in many systems, suggests it may have important and comprehensive functions in different models. In 2003, two mature forms derived from the same precursor, miR-199-s (from the 5’ half) and miR-199-as (from the 3’ half), were cloned from human osteoblast sarcoma cells and mouse skin, respectively [1]. The identity of miR-199a was computationally predicted, based on its conservation among human, mouse and puffer fish [4]. Later it was shown that both mature forms are expressed in humans, and it was renamed miR-199a-5p and miR-199a-3p, respectively [5]. (miR-199a-2, miRBase Accession MI0000281) and the other on Chromosome 19 (miR-199a-1, miRBase Accession MI0000242)
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