<p>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 <i>MIR155</i> as a potent inducer of autophagy. Enforced expression of <i>MIR155</i> increases autophagic activity in human nasopharyngeal cancer and cervical cancer cells. Knocking down endogenous <i>MIR155</i> inhibits hypoxia-induced autophagy. We demonstrated that <i>MIR155</i> targets multiple players in MTOR signaling, including <i>RHEB</i>, <i>RICTOR,</i> and <i>RPS6KB2</i>. <i>MIR155</i> suppresses target-gene expression by directly interacting with their 3′ untranslated regions (UTRs), mutations of the binding sites abolish their <i>MIR155</i> responsiveness. Furthermore, by downregulating MTOR signaling, <i>MIR155</i> also attenuates cell proliferation and induces G<sub>1</sub>/S cell cycle arrest. Collectively, these data present a new role for <i>MIR155</i> as a key regulator of autophagy via dysregulation of MTOR pathway.</p
