Identification of micro RNA-regulated autophagic pathways in plant lectin-induced cancer cell death.

Objectives 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. Micro RNAs (mi RNAs), 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 mi RNAs regulate autophagic pathways in plant lectin-induced cancer cells, still remains an enigma. Materials and methods Identification of micro RNA-regulated autophagic pathways was carried out using a series of elegant systems - biology and bioinformatics approaches, such as network construction, hub protein identification, targeted micro RNA 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 mi RNAs, 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 mi RNAs, 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. [ABSTRACT FROM AUTHOR]