MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT - PubMed (original) (raw)

. 2009 Sep 1;8(17):2756-68.

doi: 10.4161/cc.8.17.9387. Epub 2009 Sep 29.

Hong Sun, Hongyue Dai, Ryan M Walsh, Maki Imakura, Janell Schelter, Julja Burchard, Xudong Dai, Aaron N Chang, Robert L Diaz, Joseph R Marszalek, Steven R Bartz, Michael Carleton, Michele A Cleary, Peter S Linsley, Carla Grandori

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MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT

Zhan Zhang et al. Cell Cycle. 2009.

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Abstract

The hypoxia-inducible factor (HIF) pathway is essential for cell survival under low oxygen and plays an important role in tumor cell homeostasis. We investigated the function of miR-210, the most prominent microRNA upregulated by hypoxia and a direct transcriptional target of HIFs. miR-210 expression was elevated in multiple cancer types and correlated with metastasis of breast and melanoma tumors. miR-210 overexpression in cancer cell lines bypassed hypoxia-induced cell cycle arrest and partially reversed the hypoxic gene expression signature. We identified MNT, a known MYC antagonist, as a miR-210 target. MNT mRNA contains multiple miR-210 binding sites in the 3' UTR and its knockdown phenocopied miR-210 overexpression. Furthermore, loss of MYC abolished miR-210-mediated override of hypoxia-induced cell cycle arrest. Comparison of miR-210 and MYC overexpression with MNT knockdown signatures also indicated that miR-210 triggered a "MYC-like" transcriptional response. Thus, miR-210 influences the hypoxia response in tumor cells through targeting a key transcriptional repressor of the MYC-MAX network.

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