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Autophagy. 2014 Jan;10(1):70-9. doi: 10.4161/auto.26534. Epub 2013 Nov 11.

Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway.

Author information

  • 1School of Life Sciences; Tsinghua University; Beijing, China; Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
  • 2Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
  • 3School of Pharmacy; Shanghai University of Traditional Chinese Medicine; Shanghai, China.
  • 4The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
  • 5Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto, ON CA.

Abstract

Hypoxia activates autophagy, an evolutionarily conserved cellular catabolic process. Dysfunction in the autophagy pathway has been implicated in an increasing number of human diseases, including cancer. Hypoxia induces upregulation of a specific set of microRNAs (miRNAs) in a variety of cell types. Here, we describe hypoxia-induced MIR155 as a potent inducer of autophagy. Enforced expression of MIR155 increases autophagic activity in human nasopharyngeal cancer and cervical cancer cells. Knocking down endogenous MIR155 inhibits hypoxia-induced autophagy. We demonstrated that MIR155 targets multiple players in MTOR signaling, including RHEB, RICTOR, and RPS6KB2. MIR155 suppresses target-gene expression by directly interacting with their 3' untranslated regions (UTRs), mutations of the binding sites abolish their MIR155 responsiveness. Furthermore, by downregulating MTOR signaling, MIR155 also attenuates cell proliferation and induces G 1/S cell cycle arrest. Collectively, these data present a new role for MIR155 as a key regulator of autophagy via dysregulation of MTOR pathway.

KEYWORDS:

MTOR; RHEB; RICTOR; RPS6KB2; autophagy; hypoxia; microRNA

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