title: In silico analysis of molecular mechanisms of legume lectin-induced apoptosis in cancer cells.
abstract: OBJECTIVE
  The legume lectin family, one of the most extensively studied plant lectin families, has received increasing attention for the remarkable anti-tumor activities of its members for binding specific cancer cell surface glycoconjugates. MicroRNAs, a class of small, non-coding RNAs, control translation and stability of mRNAs at post-transcriptional and translational levels. To date, accumulating evidence has revealed that microRNAs are involved in progression of a number of human diseases, especially cancers. However, the molecular manners of microRNA-modulated apoptosis in legume lectin-treated cancer cells are still under investigation.
  
  
  METHODS
  We performed in silico analyses to study the interactions between three typical legume lectins (ConA, SFL and SAL) and some specific sugar-containing receptors (for example, EGFR, TNFR1, HSP70 and HSP90). Additionally, we predicted some relevant microRNAs which could significantly regulate these aforementioned targetreceptors and thus inhibiting down-stream cancer-related signaling pathways.
  
  
  RESULTS
  The results showed that these three legume lectins could competitively bind sugar-containing receptors such as EGFR, TNFR1, HSP70 and HSP90 in two ways, via anti-apoptotic or survival pathways. On the one hand, the legume lectins could induce cancer cell death through triggering receptor-mediated signaling pathways, which resulted from indirect binding between legume lectins and mannoses resided in receptors. On the other hand, direct binding between legume lectins and receptors could lead to steric hindrance, which would disturb efficient interactions between them, and thus, the legume lectins would induce cancer cell death by triggering receptor-mediated signaling pathways. In addition, we identified several relevant microRNAs that regulated these targeted receptors, thereby ultimately causing cancer cell apoptosis.
  
  
  CONCLUSIONS
  These findings provide new perspectives for exploring microRNA-modulated cell death in legume lectin-treated cancer cells, which could be utilized in combination therapy for future cancer drug development.
authors.affiliation: School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, Sichuan University, Chengdu, 610064, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Shi
authors.forename: N
authors.initials: N
authors.lastname: An
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: J K
authors.initials: JK
authors.lastname: Bao
authors.forename: B S
authors.initials: BS
authors.lastname: Yue
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D003208:Concanavalin A / Q000737:chemistry / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D007887:Fabaceae / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000494:pharmacology*; D035683:MicroRNAs / Q000378:metabolism; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry / Q000378:metabolism; D029909:Sophora / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D037102:Lectins; D035683:MicroRNAs; D047888:Receptors, Tumor Necrosis Factor, Type I; D003208:Concanavalin A; D066246:ErbB Receptors