title: Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death.
abstract: OBJECTIVE
  Plant lectins, carbohydrate-binding proteins of non-immune origin, have recently been reported to induce programmed cell death (including apoptosis and autophagy) in many types of cancer cells. MicroRNAs (miRNAs), small, non-coding endogenous RNAs, ~22 nucleotides (nt) in length, have been well characterized to play essential roles in regulation of the autophagy process in cancer; however, how these miRNAs regulate autophagic pathways in plant lectin-induced cancer cells, still remains an enigma.
  
  
  METHODS
  Identification of microRNA-regulated autophagic pathways was carried out using a series of elegant systems - biology and bioinformatics approaches, such as network construction, hub protein identification, targeted microRNA prediction, microarray analyses and molecular docking.
  
  
  RESULTS
  We computationally constructed the human autophagic protein-protein interaction (PPI) network, and further modified this network into a plant lectin-induced network. Subsequently, we identified 9 autophagic hub proteins and 13 relevant oncogenic and tumour suppressive miRNAs, that could regulate these aforementioned targeted autophagic hub proteins, in human breast carcinoma MCF-7 cells. In addition, we confirmed that plant lectins could block the sugar-containing receptor EGFR-mediated survival pathways, involved in autophagic hub proteins and relevant miRNAs, thereby ultimately culminating in autophagic cell death.
  
  
  CONCLUSIONS
  These results demonstrate that network-based identification of microRNAs modulate autophagic pathways in plant lectin-treated cancer cells, which may shed new light on the discovery of plant lectins as potent autophagic inducers, for cancer drug discovery.
authors.affiliation: School of Life Sciences, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Fu
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: H-L
authors.initials: HL
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Wen
authors.forename: S-Y
authors.initials: SY
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: J-K
authors.initials: JK
authors.lastname: Bao
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D055808:Drug Discovery / Q000379:methods; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D037121:Plant Lectins / Q000494:pharmacology* / Q000627:therapeutic use; D060066:Protein Interaction Maps / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D037121:Plant Lectins