mir-15 microRNA precursor family
| mir-15 microRNA precursor family | |
|---|---|
| SO | SO:0001244 |
| PDB structures | PDBe |
The miR-15
miR-15a/16-1 deletion has been shown to accelerate the proliferation of both human and mouse B-cells through modulation of the expression of genes controlling cell cycle progression.[5] Studies have found the miR-15a/16-1 microRNA cluster to function as a tumour suppressor, with the oncogene BCL2 as its target.[6] Specifically, miR-15a/16-1 downregulates BCL2 expression and is itself deleted or downregulated in tumour cells.[7] There is a marked increase in BCL2 levels observed in advanced prostate tumour cases, which is inversely correlated with miR-15a/16-1 expression (and so corresponds to a decrease in miR-15a/16-1 levels). Inhibition of cell proliferation by the miR-15a/16-1 cluster occurs in both lymphoid and non-lymphoid tissue.[6]
The miR-15a/16-1 cluster has further been found to be highly expressed in CD5+ cells, therefore hinting at an important role of miR-15/16 in normal CD5+ B-cell homeostasis.[3]
CHEK1
The CHEK1 (checkpoint kinase 1) gene, located at chromosome position 11q24.2, is responsible for encoding the protein kinase
Neonatal cardiomyocyte arrest
Postnatal heart development sees the upregulation of multiple miR-15 family members. In particular, miR-195, when found at higher levels than normal in the developing heart, has been identified as a factor that may cause heart abnormalities in newborns.[1] This has been linked to premature cell cycle arrest, through impaired proliferation of heart muscle fibres and through repressed mitotic gene expression.[9] An accumulation of cardiac muscle fibres sees a consequent block in the transition between the pre-mitotic/G2 phase and mitotic phase of the cell cycle, with postnatal inhibition of the miR-15 family inducing cardiac muscle fibres to enter mitosis. miR-195 overexpression is further associated with cellular hypertrophy.[10]
References
Further reading
- Finnerty JR, Wang WX, Hébert SS, Wilfred BR, Mao G, Nelson PT (August 2010). "The miR-15/107 Group of MicroRNA Genes: Evolutionary Biology, Cellular Functions, and Roles in Human Diseases". J Mol Biol. 402 (3): 491–509. PMID 20678503.
- Cimmino A, Calin GA, Fabbri M, et al. (September 2005). "miR-15 and miR-16 induce apoptosis by targeting BCL2". Proc. Natl. Acad. Sci. U.S.A. 102 (39): 13944–9. PMID 16166262.
- Palamarchuk A, Efanov A, Nazaryan N, et al. (May 2010). "13q14 deletions in CLL involve cooperating tumor suppressors". Blood. 115 (19): 3916–22. PMID 20071661.
- Aqeilan RI, Calin GA, Croce CM (February 2010). "miR-15a and miR-16-1 in cancer: discovery, function and future perspectives". Cell Death Differ. 17 (2): 215–20. PMID 19498445.
- Guo CJ, Pan Q, Li DG, Sun H, Liu BW (April 2009). "miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis". J. Hepatol. 50 (4): 766–78. PMID 19232449.
- Xia L, Zhang D, Du R, et al. (July 2008). "miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells". Int. J. Cancer. 123 (2): 372–9. PMID 18449891.
External links