Hypoxia-induced miR-424 decreases tumor sensitivity to chemotherapy by inhibiting apoptosis

被引:0
|
作者
D Zhang
Z Shi
M Li
J Mi
机构
[1] Shanghai Key Laboratory of Tumor Microenvironment and Inflammation,Department of Biochemistry & Molecular Cell Biology
[2] Shanghai Jiao Tong University School of Medicine,undefined
[3] Institute of Cancer Stem Cell,undefined
[4] Dalian Medical University,undefined
来源
Cell Death & Disease | 2014年 / 5卷
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摘要
Chemotherapy resistance of tumor cells is a big challenge. Adaption to hypoxia is an essential cellular response that is controlled by the master oxygen-sensitive transcription factor HIF1 (hypoxia-inducible factor 1). The mechanism by which tumor cells acquire resistance to chemotherapy under hypoxic conditions is not fully understood. In this study, we found that hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3′ untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 enhanced apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples. These results suggest that miR-424 is a potential molecular target for tumor therapy.
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页码:e1301 / e1301
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