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

Cell Death and Disease, ISSN: 2041-4889, Vol: 5, Issue: 6, Page: e1301
2014
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Article Description

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. © 2014 Macmillan Publishers Limited All rights reserved.

Bibliographic Details

D. Zhang; Z. Shi; J. Mi; M. Li

Springer Science and Business Media LLC

Immunology and Microbiology; Neuroscience; Biochemistry, Genetics and Molecular Biology

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