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MiR‐92a mediates AZD6244 induced apoptosis and G1‐phase arrest of lymphoma cells by targeting Bim
Author(s) -
Lv XiaoBin,
Zhang Xing,
Deng Lan,
Jiang Ling,
Meng Wei,
Lu Zhigang,
Wang Xiuju
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10225
Subject(s) - apoptosis , cancer research , downregulation and upregulation , gene silencing , microbiology and biotechnology , kinase , biology , biochemistry , gene
AZD6244, an ATP‐uncompetitive inhibitor of mitogen‐activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours. However, whether AZD6244 has a function in lymphoma cells is not known. We report that AZD6244 treatment represses the growth of Raji and MOLT4 cells by inducing apoptosis and G1‐phase arrest. Using miRNAs array and quantitative RT‐PCR, miR‐92a was downregulated byAZD6244 treatment through the ERK1/2‐AP1 signalling pathway. Overexpression of miR‐92a abrogated AZD6244‐induced apoptosis and G1‐phase arrest, indicating that it is involved in the cytotoxicity of AZD6244 in lymphoma cells. A luciferase reporter assay showed that miR‐92a directly targetsthe 3′‐UTRs of Bim. Overexpression of miR‐92a mimics downregulated Bim mRNA and protein expression level, indicating that miR‐92a negatively regulates its expression at both levels. Silencing Bim decreases AZD6244‐induced apoptosis and G1‐phase arrest, suggesting that Bim contributes to the growth arrest. Thus, miR‐92a mediates AZD6244‐induced cytotoxicity of lymphoma cells by targeting Bim. Downregulation of miR‐92a by AZD6244 is mediated by the ERK1/2‐AP1 signalling pathway.