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

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.

Prognostic characterization of OAS1/OAS2/OAS3/OASL in breast cancer

“…Marino et al demonstrated that OAS1 was able to affect cell migration [28]. Moreover, OASL was considerably related to cancer proliferation [26]. Our data highlighted the prognostic values of OAS members in mRNA expression and DNA methylation, as well as the gene signature, enabling multilevel insights for these prognostic predictors.…”

“…Previously, OAS family members have been found to be involved in a variety of diseases, including infections, autoimmune disorders and cancer. Their functions include antiviral modulation, apoptosis control, cell growth, differentiation and gene regulation [19][20][21][22][23][24][25][26]. In 1986, Liu et al reported a potential correlation between OAS activity and tumor growth in human mammary tumors [27].…”

Oligoadenylate synthetases-like is a prognostic biomarker and therapeutic target in pancreatic ductal adenocarcinoma

“…The OAS families, of which OASL is a member, have been found correlated with multiple diseases, including infections, autoimmune disorders, and cancers (22)(23)(24). In particular, it has been reported that OASL is significantly related to tumor proliferation (10). Our data highlighted the prognostic value and therapeutic target of OASL in PDCA.…”

“…The role of OASL in tumor itself is rarely reported. Studies have shown that OASL is closely related to the proliferation of various tumors (10). In addition, OASL has been identified as a pivotal gene of trastuzumab-resistant gastric cancer (11).…”

Evidence of Extensive Intraspecific Noncoding Reshuffling in a 169-kb Mitochondrial Genome of a Basidiomycetous Fungus

“…Of these, group IB introns accounted for 57.4% of total introns (70/122). Interestingly, the 13th intron of P. noxius cox1 gene (cox1_intron13) was predicted to have two separated complete intron cores (IB and ID) suggesting a twintron: an intron inserted by another intron (Deng et al. 2018).…”