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 RNA s (mi RNA s), small, non‐coding endogenous RNA s, ∼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 RNA s 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 RNA s, 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 RNA s, 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.