Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional pattern of E. coli BW25113 and its ptsA, glpK and dhaKLM isogenic mutants growing on DHA (dihydroxyacetone).

ABSTRACT: Dihydroxyacetone (DHA) is an attractive molecule produced in a wide range of industries . DHA is found among all the kingdoms as an intermediate of various metabolic pathways and can be used as a carbon source by many organisms. The bacterium Escherichia coli is able to grow on DHA as the sole carbon source albeit at a low growth rate (0.1 h-1). If the topology of DHA metabolic network has been characterized, the function and regulation of the metabolic pathways involved in DHA metabolism remain unsolved. Here, we aimed to better understand DHA metabolism in E. coli BW25113 by exploring its transcriptional pattern on DHA versus glucose. We also studied the pattern of three DHA pathway mutants (dhaKLM, ptsA and glpK).

ORGANISM(S): Escherichia coli K-12

SUBMITTER: Brice Enjalbert

PROVIDER: E-MTAB-7666 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.

Dataset Information

Transcriptional pattern of E. coli BW25113 and its ptsA, glpK and dhaKLM isogenic mutants growing on DHA (dihydroxyacetone).

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