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

Authors
  • Zhang, D
  • Shi, Z
  • Li, M
  • Mi, J
Type
Published Article
Journal
Cell Death and Disease
Publisher
Springer Nature
Publication Date
Jan 01, 2014
Volume
5
Identifiers
DOI: 10.1038/cddis.2014.240
PMID: 24967963
Source
Medline
License
Unknown

Abstract

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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