Identification of Novel Pathways in Plant Lectin-Induced Cancer Cell Apoptosis

Our plain-English summary of Identification of Novel Pathways in Plant Lectin-Induced Cancer Cell Apoptosis, by Z. Shi, R. Sun, T. Yu, et al (International Journal of Molecular Sciences, 2016).

The study

• Authors: Z. Shi, R. Sun, T. Yu, R. Liu, L.J. Cheng, J.K. Bao, L. Zou, Y. Tang
• Journal: International Journal of Molecular Sciences
• Published: 2016;17(2):228
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Plant lectins have been investigated to elucidate their complicated mechanisms due to their remarkable anticancer activities. Although plant lectins seems promising as a potential anticancer agent for further preclinical and clinical uses, further research is still urgently needed and should include more focus on molecular mechanisms. Herein, a Naïve Bayesian model was developed to predict the protein-protein interaction (PPI), and thus construct the global human PPI network. Moreover, multiple sources of biological data, such as smallest shared biological process (SSBP), domain-domain interaction (DDI), gene co-expression profiles and cross-species interolog mapping were integrated to build the core apoptotic PPI network. In addition, we further modified it into a plant lectin-induced apoptotic cell death context. Then, we identified 22 apoptotic hub proteins in mesothelioma cells according to their different microarray expressions. Subsequently, we used combinational methods to predict microRNAs (miRNAs) which could negatively regulate the abovementioned hub proteins. Together, we demonstrated the ability of our Naïve Bayesian model-based network for identifying novel plant lectin-treated cancer cell apoptotic pathways. These findings may provide new clues concerning plant lectins as potential apoptotic inducers for cancer drug discovery.

In plain English

This was a computer-based study, not a study of asbestos or of people. The authors used a statistical method (a Naïve Bayesian model) and public databases to map how human proteins interact. They then narrowed it to proteins involved in apoptosis (programmed cell death). Their reference set held 85,083 unique protein interactions (13,128 proteins), and the predicted core apoptosis network held 3767 protein pairs. They focused on proteins that earlier reports linked to cell death caused by plant lectins (plant proteins). They used an existing gene-activity dataset from mesothelioma cells treated with the drugs piroxicam and cisplatin, compared with a control group. Combining this with their network, they identified 22 hub proteins whose genes differed in activity: nine genes were up-regulated and 13 down-regulated. Three prediction programs listed microRNAs that might suppress some of these proteins. For caspase-9, five microRNAs appeared in the combined result. The authors concluded that the pathways identified might shed new light on developing plant lectins as cancer drugs. The article does not say what caused the mesothelioma or which type it was.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Computational (in silico) network analysis: a Naïve Bayesian model built a predicted human protein-protein interaction network. It was combined with a re-analysis of an existing microarray dataset and with microRNA target-prediction programs.
• Who was studied: No people or animals were studied directly. The data came from public protein-interaction databases (BioGRID, HomoMINT, HPRD, BOND, IntAct) and from a public microarray dataset (E-GEOD-22445) of mesothelioma cells treated with piroxicam/cisplatin compared with a control group, run three times in each group. No dates or locations of the original samples are given.
• Exposure: No asbestos exposure was studied. The 'plant lectin' context was built from proteins that earlier reports had linked to plant lectin-induced cancer cell apoptosis. The mesothelioma cells in the microarray data were treated with piroxicam/cisplatin, not with lectins.
• Main results:
  • The reference (Gold Standard Positive) set contained 85,083 unique protein-protein interactions involving 13,128 proteins.
  • The predicted core apoptotic sub-network consisted of 3767 protein pairs.
  • The extracted hub proteins were grouped into four protein families: Bcl-2, caspase, MAPK and p53.
  • The network analysis was combined with the gene-expression data from piroxicam/cisplatin-treated mesothelioma cells. Together these identified 22 hub proteins whose genes showed different expression: nine genes up-regulated and 13 down-regulated. These are gene-expression results, not protein measurements.
  • For caspase-9, the programs predicted 51 (Diana-MicroH), 14 (miRanda) and 156 (TargetScan) microRNAs. Five appeared in the consensus (hsa-miR-124, hsa-miR-182, hsa-miR-504, hsa-miR-506, hsa-miR-96) and may negatively regulate caspase-9 signaling. Consensus microRNAs were also listed for RIPK2, GRB2, CDK2, CASP8 and RAF1.
  • In the predicted network, CASP8 was associated with BCL10 and RIPK2.
• The authors' conclusion: The authors concluded that the novel pathways they identified might shed new light on developing plant lectins as apoptosis inducers for future cancer drugs.

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Mesothelioma, Discovery.

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