Simulation study of cDNA dataset to investigate possible association of differentially expressed genes of human THP1-monocytic cells in cancer progression affected by bacterial shiga toxins

Syed A. Muhammad, Jinlei Guo, Thanh M. Nguyen, Xiaogang Wu, Baogang Bai, X. Yang, Jake Y. Chen

Research output: Contribution to journalArticle

Abstract

Shiga toxin (Stxs) is a family of structurally and functionally related bacterial cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively. Until recently, it has been thought that Stxs only inhibits the protein synthesis and induces expression to a limited number of genes in host cells, but recent data showed that Stxs can trigger several signaling pathways in mammalian cells and activate cell cycle and apoptosis. To explore the changes in gene expression induced by Stxs that have been shown in other systems to correlate with cancer progression, we performed the simulated analysis of cDNA dataset and found differentially expressed genes (DEGs) of human THP1-monocytic cells treated with Stxs. In this study, the entire data (treated and untreated replicates) was analyzed by statistical algorithms implemented in Bioconductor packages. The output data was validated by the k-fold cross technique using generalized linear Gaussian models. A total of 50 DEGs were identified. 7 genes including TSLP, IL6, GBP1, CD274, TNFSF13B, OASL, and PNPLA3 were considerably (< 0.00005) related to cancer proliferation. The functional enrichment analysis showed 6 down-regulated and 1 up-regulated genes. Among these DEGs, IL6 was associated with several cancers, especially with leukemia, lymphoma, lungs, liver and breast cancers. The predicted regulatory motifs of these genes include conserved RELA, STATI, IRFI, NF-kappaB, PEND, HLF, REL, CEBPA, DI_2, and NFKB1 transcription factor binding sites (TFBS) involved in the complex biological functions. Thus, our findings suggest that Stxs has the potential as a valuable tool for better understanding of treatment strategies for several cancers.

Original languageEnglish (US)
Article number380
JournalFrontiers in Microbiology
Volume9
Issue numberMAR
DOIs
StatePublished - Mar 1 2018

Fingerprint

Shiga Toxins
Complementary DNA
Genes
Neoplasms
NF-kappa B p50 Subunit
Interleukin-6
Shigella dysenteriae
Shiga Toxin
Bacillary Dysentery
NF-kappa B
Cytotoxins
Colitis
Regulator Genes
Liver Neoplasms
Datasets
Linear Models
Lymphoma
Lung Neoplasms
Cell Cycle
Leukemia

Keywords

  • Cancers
  • cDNA dataset
  • Differential expression
  • Enrichment analysis
  • Shiga toxin
  • TFBS

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Simulation study of cDNA dataset to investigate possible association of differentially expressed genes of human THP1-monocytic cells in cancer progression affected by bacterial shiga toxins. / Muhammad, Syed A.; Guo, Jinlei; Nguyen, Thanh M.; Wu, Xiaogang; Bai, Baogang; Yang, X.; Chen, Jake Y.

In: Frontiers in Microbiology, Vol. 9, No. MAR, 380, 01.03.2018.

Research output: Contribution to journalArticle

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