MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene
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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.
KeywordsmiR-142-3p MLL-AF4 Acute lymphoblastic leukemia MicroRNA
Acute lymphoblastic leukemia
This work was supported by the Beijing Nova Program (2011114), National Natural Science Foundation of China (Nos. 30800482, 30971297, 81102242,81000221, 81270610 and 90919044), the Beijing Natural Science Foundation of China (No. 7102147 and 7132217), High and New Technology Program of the PLA (2010gxjs091), Capital Medical Development Scientific Research Fund (No. 2007-2040), National Public Health Grand Research Foundation (No. 201202017), the funding of the public health project (Z111107067311070), and the National 973 Project of China (No. 2005CB522400).
Conflict of interest
The authors declare that there is no conflict of interest.
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