- MicroRNA: Biogenetic and Functional Mechanisms and Involvements in Cell Differentiation and Cancer
Increasing evidence indicates that miRNAs have distinct expression patterns among tissues and cells in different differentiation stage (25). It is reported that overexpression of miR-124, which is preferentially expressed in brain, shifted the gene expression profile of HeLa cells towards that of the brain. Similarly, overexpression of miR-1 shifted the expression profile towards that of the muscle in that miR-1 is preferentially expressed (25). These results indicate that miRNAs play important roles in cell differentiation and characterization. Recently, it was revealed that miRNAs also played critical roles in the differentiation of mammalian hematopoietic lineage. For example, miR-181 is preferentially expressed in the thymus and B-lymphoid cells of mouse bone marrow and promotes B cell differentiation by overexpression in hemapoietic stem/progenitor cells (26). Conversely, overexpression of the miR-181a, one member of the miR-181 family, was reported to repress megakaryoblast differentiation in humans (27). By the induction of megakaryoblast differentiation, the expression of endogenous miR-181a is downregulated through the acetylcholinesterase, protein kinase (PK) C, and PKA cascade. The expression of miR-130a is also downregulated by the induction of megakaryoblast differentiation (28). miR-130a targets the transcriptional factor MAFB that is a transcriptional activator of GPIIB, an important protein for platelet physiology. Furthermore, miR-223 is upregulated by the retinoic acid-induced replacement of NFI-A with CCAAT/Enhancer binding protein (C/EBP) α, and promotes human granulopoiesis (29). As miR-223 repressed NFI-A translation, the upregulation of miR-223 by C/EBPα and granulopoiesis further accelerated through positive feedback by miR-223.
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