Kinases as targets including both tyrosine and serine-threonine kinases

Overexpression of miRNA-1 in the mouse developing heart has a negative effect on CHIR-99021 muscle proliferation as it targets the transcription factor that promotes ventricular cardiomyocyte expansion, Hand2. In Drosophila, the expression of miR-1 is controlled by the Twist and Mef2 transcription factors. Investigation of a loss-of-function phenotype of Drosophila miR-1 showed that miR-1 is not required for the formation or physiological function of the larval musculature, but is required for the post-mitotic growth of larval muscle. Recent studies showed that miR-1 promotes myogenesis by targeting histone deacetylase 4, a transcriptional repressor of muscle gene expression, and that miR-133 enhances myoblast proliferation by repressing serum response factor, both examples of new molecular mechanisms to regulate skeletal muscle gene expression and embryonic developmental. Another miRNA, miR-206, has also been characterized as a muscle regulator in recent studies. In co-operation with miR-133, miR-206 can repress myoblast fusion by targeting the connexin 43 gap junction channels without altering the Cx43 mRNA level. These findings have generated more detailed insights into the mechanisms underlying the myogenesis process and have uncovered different pathways that lead to myofiber proliferation and differentiation. However, the complete roles of miRNAs in muscle growth & development still remain to be elucidated. In mammals, muscle mass is mainly KRX-0401 determined by the number and size of muscle fibers. In the pig, for example, the number of muscle fibers is prenatally determined during primary and secondary muscle fiber formation, while the postnatal hypertrophy process then increases the length and diameter of these fibers. Primary muscle fiber formation begins at approximately 30 days following gestation. Secondary muscle fiber formation begins at about 50 to 60 days post-gestation, when myoblasts align and fuse to form secondary muscle fibers at the surface of existing primary muscle fibers. Identification of genes governing these processes will provide insights into the regulation of muscle growth. Currently, numerous genes, including growth factors, regulatory proteins, receptors, and transcription factors have been identified as participating in the regulation of the myogenesis. However, the underlying molecular pathway elements, such as the decisive secondary regulatory factors of the major genes responsible for controlling prenatal muscle growth, remains poorly understood. We hypothesized that there were more miRNAs associated with muscle growth and development in prenatal pigs yet to be discovered. Profiling of transcriptome changes of mature miRNAs isolated from key developmental stages is a promising technique to use in uncovering these miRNAs.

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