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Mol Biol Rep. 2013 Dec;40(12):6811-9. doi: 10.1007/s11033-013-2798-6. Epub 2013 Sep 22.

MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene.

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1
Department of Hematology, Chinese PLA General Hospital, Fuxing Road 28th, Beijing, 100853, China.

Abstract

The mixed-lineage leukemia (MLL)-AF4 fusion protein encoded by the chromosomal translocation t(4;11) predicts a poorer prognosis in acute lymphoblastic leukemia (ALL) than in other MLL-associated leukemias. However, the detailed mechanism underlying regulation of MLL-AF4 expression remains largely unknown. In this study, we showed that microRNA (miR)-142-3p was significantly downregulated in ALL patients expressing MLL-AF4. Upregulation of miR-142-3p decreased MLL-AF4 expression in the RS4;11 leukemic cell line, which suggests that MLL-AF4 is a direct target of miR-142-3p. Ectopic expression of miR-142-3p remarkably suppressed cell proliferation and induced apoptosis in RS4;11 cells expressing the MLL-AF4 fusion protein. We also found that exogenous expression of miR-142-3p strongly reduced the expression of MLL-AF4 target genes such as homeobox A (HOXA)9, HOXA7, and HOXA10 in RS4;11 cells. Taken together, our results indicate that miR-142-3p functions as a growth suppressor in MLL-AF4(+) ALL, and its suppressive effects are mediated primarily through repression of MLL-AF4 expression.

PMID:
24057258
DOI:
10.1007/s11033-013-2798-6
[Indexed for MEDLINE]
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