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The mature products are thought to exert regulatory roles by binding with partial complementarity to microRNA recognition elements (MREs) in the 3' untranslated region (3' UTR) of target transcripts. Experimental evidence suggests that putative targets of mature miR-29 products include the following:
miR-29a and -29b have been shown to regulate critical apoptotic genes in AML cell lines. Amongst these is the MCL1 gene, coding for the MCL1 protein. Myeloid leukaemia cell differentiation protein (MCL1) is a potent multi-domain anti-apoptotic protein belonging to the BCL2 family of proteins.[1] miR-29b has been found to downregulate MCL1 protein levels, and MCL1 upregulation is consistent with reduced miR-29b expression in malignant cells.
A tight regulation of MCL1 is important, as insufficient MCL1 levels can result in cell death whilst overexpression leads to cellular transformation. [2] MCL1 overexpression is commonly seen in cancers.[3]
Such MCL1 upregulation in malignant cells is consistent with reduced miR-29b expression, as miR-29b downregulates MCL1 cellular protein levels. It also sensitises cancer cells to apoptosis, specifically to tumour-necrosis-factor-related apotosis-inducing ligand (TRAIL) cytotoxicity.[1] It has been found that miR-29b does not affect MCL1 miRNA expression.
miR-29b targets apoptosis, cell cycle and proliferation pathways.[4] miR-29b is deregulated in acute myelogenous leukaemia (AML) in primary AML precursor cells.
- ^ a b Mott JL, Kobayashi S, Bronk SF, Gores GJ (2007). "mir-29 regulates Mcl-1 protein expression and apoptosis". Oncogene. 26 (42): 6133–6140. doi:10.1038/sj.onc.1210436. PMC 2432524. PMID 17404574.
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: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid17404574" was defined multiple times with different content (see the help page). - ^ Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S; et al. (2006). "Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia". Cancer Cell. 10 (5): 375–88. doi:10.1016/j.ccr.2006.10.006. PMID 17097560.
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(help)CS1 maint: multiple names: authors list (link) - ^ Sieghart W, Losert D, Strommer S, Cejka D, Schmid K, Rasoul-Rockenschaub S; et al. (2006). "Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy". J Hepatol. 44 (1): 151–7. doi:10.1016/j.jhep.2005.09.010. PMID 16289418.
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(help)CS1 maint: multiple names: authors list (link) - ^ Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T; et al. (2009). "MicroRNA 29b functions in acute myeloid leukemia". Blood. 114 (26): 5331–41. doi:10.1182/blood-2009-03-211938. PMC 2796138. PMID 19850741.
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(help)CS1 maint: multiple names: authors list (link)