title: MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells.
abstract: Autophagy is an evolutionarily conserved, multi-step lysosomal degradation             process in which a cell degrades its own long-lived proteins and damaged organelles.             Ataxia telangiectasia mutated (ATM) has recently been shown to upregulate the             process of autophagy. Previous studies showed that certain microRNAs, including             miR-18a, potentially regulate ATM in cancer cells. However, the mechanisms behind             the modulation of ATM by miR-18a remain to be elucidated in colon cancer cells.             In the present study, we explored the impact of miR-18a on the autophagy process             and ATM expression in HCT116 colon cancer cells. To determine whether a preliminary             link exists between autophagy and miR-18a, HCT116 cells were irradiated and quantitative             (q) PCR was performed to measure miR-18a expression. HCT116 cells were transfected             with an miR-18a mimic to study its impact on indicators of autophagy. Western             blotting and luciferase assays were implemented to explore the impact of miR-18a             on ATM gene expression in HCT116 cells. The results showed that miR-18a expression             was strongly stimulated by radiation. Ectopic overexpression of miR-18a in HCT116             cell lines potently enhanced autophagy and ionizing radiation-induced autophagy.             Moreover, miR-18a overexpression led to the upregulation of ATM expression and             suppression of mTORC1 activity. Results of the present study pertaining to the             role of miR-18a in regulating autophagy and ATM gene expression in colon cancer             cells revealed a novel function for miR-18a in a critical cellular event and on             a crucial gene with significant impacts in cancer development, progression, treatment             and in other diseases.
authors.affiliation: Department of Surgery, College of Medicine, University of Mosul,                     Mosul, Iraq.
authors.forename: Abu Baker
authors.initials: AB
authors.lastname: Qased
authors.forename: Heqing
authors.initials: H
authors.lastname: Yi
authors.forename: Nan
authors.initials: N
authors.lastname: Liang
authors.forename: Shumei
authors.initials: S
authors.lastname: Ma
authors.forename: Shixing
authors.initials: S
authors.lastname: Qiao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D064007:Ataxia Telangiectasia Mutated Proteins; D001343:Autophagy / Q000528:radiation effects*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000528:radiation effects*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; D046912:Multiprotein Complexes; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases