Micromanaging iron homeostasis: Hypoxia-inducible micro-RNA-210 suppresses iron homeostasis-related proteins

Yusuke Yoshioka, Nobuyoshi Kosaka, Takahiro Ochiya, Takashi Kato*

*この研究の対応する著者

研究成果: Article査読

56 被引用数 (Scopus)

抄録

Iron is fundamental for sustaining life for living organisms, and the iron metabolism is finely regulated at different levels. In cancer cells, deregulation of the iron metabolism induces oxidative stress and drives tumor progression and metastasis; however, the molecular mechanisms of iron homeostasis are not fully understood. Here we found that iron deficiency as well as hypoxia promoted microRNA-210 (miR-210) expression. A central mediator of miR-210 transcriptional activation is the hypoxia-inducible factor (HIF)-1α, and the hypoxia-response element in the miR-210 promoter is confirmed experimentally. This is in agreement with the data from in vivo studies that have demonstrated the presence of miR-210-expressing cells at the chronic hypoxic regions of xenografted tumors. Furthermore we found two essential molecules for iron homeostasis, iron-sulfur cluster scaffold protein (ISCU) and transferrin receptor 1 (TfR), are a direct target of miR-210. Transfection ofmiR-210decreases the uptake of transferrin by inhibiting the expression of TfR. In addition, inhibition of miR-210 by anti-miR-210 up-regulates ISCU expression. These findings suggest that miR-210 works as an iron sensor and is involved in the maintenance of iron homeostasis by sustaining the TfR expression level to stimulate cell proliferation and promote cell survival in the hypoxic region within tumors.

本文言語English
ページ(範囲)34110-34119
ページ数10
ジャーナルJournal of Biological Chemistry
287
41
DOI
出版ステータスPublished - 2012 10月 5

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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