Journal
AUTOPHAGY
Volume 10, Issue 1, Pages 70-79Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.26534
Keywords
hypoxia; autophagy; microRNA; MTOR; RHEB; RICTOR; RPS6KB2
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Funding
- China-Canada Joint Health Research Grant (National Natural Science Foundation of China and Canadian Institutes of Health Research) [81261120556]
- National Natural Science Foundation of China [31100976]
- International Cooperation Grant of Shenzhen [GJHZ2012619112804434]
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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.
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