| First Author | Ge Y | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1832 |
| Issue | 1 | Pages | 1-10 |
| PubMed ID | 23000971 | Mgi Jnum | J:192882 |
| Mgi Id | MGI:5466774 | Doi | 10.1016/j.bbadis.2012.09.004 |
| Citation | Ge Y, et al. (2013) MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways. Biochim Biophys Acta 1832(1):1-10 |
| abstractText | Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-350 in the cardiac setting is still unclear. The objective of this study is to determine whether miR-350 alone can induce pathological cardiac hypertrophy by repressing the SAPK pathway in cardiomyocytes. Here we report that miR-350 plays a key role in determining pathological cardiomyocyte hypertrophy and apoptosis. Comprehensive microarray profiling of miRs and qPCR showed that this unique miRNA was significantly up-regulated in rat hearts in response to late-stage transverse aortic constriction. Western blotting and luciferase assays confirmed that the target mRNAs of miR-350 are mitogen activated protein kinase (MAPK) 11/14 and MAPK8/9 gene transcripts. Gain-of-unction and loss-of-function approaches were used to investigate the functional roles of miR-350. The forced over-expression of miR-350 was sufficient to induce hypertrophy of cardiomyocytes through the posttranslational suppression of p38 and JNK protein synthesis. Moreover, miR-350 led to an increase in unphosphorylated NFATc3 and its nuclear translocation, resulting in the over-expression of pathological hypertrophy markers. As predicted, these effects could effectively be imitated by siR-JNK/p38 through the degeneration of p38 and JNK mRNAs. Conversely, antagomir-350 could lower the levels of miR-350, reverse the expression of target proteins and reduce cell size and apoptosis relative to the administration of mutant antagomir-350. Our data provide the first evidence that miR-350 is a critical regulator of pathological cardiac hypertrophy and apoptosis in rats. |
