L.-L. Fu, X. Zhao and H.-L. Xu contributed equally to this work.
Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death
Article first published online: 7 AUG 2012
© 2012 Blackwell Publishing Ltd
Volume 45, Issue 5, pages 477–485, October 2012
How to Cite
Fu, L.-L., Zhao, X., Xu, H.-L., Wen, X., Wang, S.-Y., Liu, B., Bao, J.-K. and Wei, Y.-Q. (2012), Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death. Cell Proliferation, 45: 477–485. doi: 10.1111/j.1365-2184.2012.00840.x
- Issue published online: 27 AUG 2012
- Article first published online: 7 AUG 2012
- Manuscript Accepted: 14 MAY 2012
- Manuscript Received: 11 FEB 2012
- Young teacher's fund of Sichuan University. Grant Number: 2010SCU11066
- Science Foundation for Post Doctorate Research of China. Grant Number: 20110491725
- Major State Basic Research Development Program of China (973 Program). Grant Number: 2010cb529900
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.
Materials and 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.
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.
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.