title: Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway.
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.
authors.affiliation: School 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Wan
authors.affiliation: Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xie
authors.affiliation: School of Pharmacy; Shanghai University of Traditional Chinese Medicine; Shanghai, China.
authors.forename: Zhenyan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmacy; Shanghai University of Traditional Chinese Medicine; Shanghai, China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Lao
authors.affiliation: School 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.
authors.forename: Nunu
authors.initials: N
authors.lastname: Huang
authors.affiliation: School 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.
authors.forename: Kai
authors.initials: K
authors.lastname: Cui
authors.affiliation: School 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.
authors.forename: Meijian
authors.initials: M
authors.lastname: Liao
authors.affiliation: Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto, ON CA.
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
authors.affiliation: School of Pharmacy; Shanghai University of Traditional Chinese Medicine; Shanghai, China.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
authors.forename: Naihan
authors.initials: N
authors.lastname: Xu
authors.affiliation: Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
authors.forename: Yaou
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D058570:TOR Serine-Threonine Kinases
keywords: MTOR; RHEB; RICTOR; RPS6KB2; autophagy; hypoxia; microRNA