Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that function as epigenetic modulators regulating almost any gene expression. Similarly, other noncoding RNAs, as well as epigenetic modifications, can regulate miRNAs. This reciprocal interaction forms a miRNA-epigenetic feedback loop, the deregulation of which affects physiological processes and contributes to a great diversity of diseases. In the present review, we focus on miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It therefore serves as a biomarker for several types of cancer, and recently has also been found to be involved in reparative processes and neural repair. In addition, we present the pleiad of functions in which miR-615 is involved, as well as their multiple target genes and the multiple regulatory molecules involved in its own expression. We do this by introducing in a comprehensible way the reported knowledge of their actions and interactions and proposing an integral view of its regulatory mechanisms.
Highlights
Homeobox genes encode transcription factors that regulate the expression of several genes during embryogenesis [1]
Among them is miR-615, which is located within the intron of the Hoxc5 gene (12q13.13). miR-615 has a restricted phylogenetic distribution and is absent in non-mammalian tetrapods but highly conserved across eutherian mammals [5], which allows it to contribute in eutherian evolution and development [6]
With the exception of some examples of hepatocellular carcinoma (HCC) [27,51], a downregulation of this miRNA has been documented in several malignancies of different lineages such as carcinomas [28,52,53], lymphomas [54] and glioblastomas [55], with an indirect relationship between the level of expression of miR-615-5p and the tumor cell capacity for proliferation, invasion, migration and angiogenesis
Summary
Homeobox genes encode transcription factors that regulate the expression of several genes during embryogenesis [1]. With the exception of some examples of HCC [27,51], a downregulation of this miRNA has been documented in several malignancies of different lineages such as carcinomas [28,52,53], lymphomas [54] and glioblastomas [55], with an indirect relationship between the level of expression of miR-615-5p and the tumor cell capacity for proliferation, invasion, migration and angiogenesis. The mechanism is achieved by direct in vivo and negative inhibition of miR-615-5p on its downstream targets IGF2 ↓[27]
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