Analyzing the differentially expressed genes and pathway cross‐talk in aggressive breast cancer

Chen, Wenyan; Wu, Fang; You, Zhenyu; Zhang, Zhanmin; Guo, Yi; Zhong, Lu-Xing

doi:10.1111/jog.12495

Cited by 22 publications

(13 citation statements)

References 32 publications

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“…Apart from dysfunctional metabolism of dicarboxylates, tyrosine degradation, initiated by the tyrosine transamination with 2-oxoglutarate [ 48 - 50 ], and glutamate exchange for cystine through x c − cystine/glutamate antiporter SLC7A11 [ 51 - 54 ], are considered important for cancer cell metabolism. Stimulation of tyrosine degradation to fumarate and acetoacetate (terminal step catalyzed by FAH, Figure 6 ), with ATP-dependent acetoacetate activation to acetoacetyl-CoA by AACS (not shown in Figure 6 ), may occur due to SP-induced increase in tyrosine transamination with accumulated 2-oxoglutarate, catalyzed by TAT (Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner

et al. 2016

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2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is often implied to be inactive in cancer, but this was not experimentally tested. We addressed the question through specific inhibition of OGDH by succinyl phosphonate (SP). SP action on different cancer cells was investigated using indicators of cellular viability and reactive oxygen species (ROS), metabolic profiling and transcriptomics. Relative sensitivity of various cancer cells to SP changed with increasing SP exposure and could differ in the ATP- and NAD(P)H-based assays. Glioblastoma responses to SP revealed metabolic sub-types increasing or decreasing cellular ATP/NAD(P)H ratio under OGDH inhibition. Cancer cell homeostasis was perturbed also when viability indicators were SP-resistant, e.g. in U87 and N2A cells. The transcriptomics database analysis showed that the SP-sensitive cells, such as A549 and T98G, exhibit the lowest expression of OGDH compared to other TCA cycle enzymes, associated with higher expression of affiliated pathways utilizing 2-oxoglutarate. Metabolic profiling confirmed the dependence of cellular SP reactivity on cell-specific expression of the pathways. Thus, oxidative decarboxylation of 2-oxoglutarate is significant for the interdependent homeostasis of NAD(P)H, ATP, ROS and key metabolites in various cancer cells. Assessment of cell-specific responses to OGDH inhibition is of diagnostic value for anticancer strategies.

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Section: Resultsmentioning

confidence: 99%

Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner

et al. 2016

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“…Calcium ions play a vital role in muscle contraction, neuronal transmission, cell motility, cell growth or proliferation [ 24 – 27 ]. It has been reported that calcium signaling pathway is related to progression and development of various cancers including lung adenocarcinoma [ 28 ], colorectal cancer [ 29 ], glioblastoma [ 30 ], breast cancer [ 31 ], and Burkitt lymphoma [ 32 ]. Calcium signaling pathway may play a key role in the progression and development of AML.…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA-mRNA Network Associated with Acute Myeloid Leukemia Survival

Zhang

Bai

Zhu³

et al. 2017

Med Sci Monit

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BackgroundAcute myeloid leukemia (AML) is a common hematologic malignancy of adults. The pathophysiological mechanism of AML is not well understood. The purpose of this study was to examine the crucial miRNAs and mRNAs associated with AML survival.Material/MethodsThe full clinical dataset of miRNA and mRNA expression profiling of AML patients was downloaded from The Cancer Genome Atlas database. Univariate Cox regression analysis was performed to obtain those miRNAs and mRNAs associated with AML survival. A miRNA-mRNA interaction network was constructed. The underlying functions of mRNAs were predicted through Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway enrichment. The expression levels of miRNAs and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsFourteen miRNAs and 830 mRNAs associated with AML survival were identified. Of the 14 miRNAs, hsa-mir-425, hsa-mir-1201, and hsa-mir-1978 were identified as risk factors and the other 11 miRNAs were identified as protective factors of AML survival. For target-genes of miRNAs, GTSF1, RTN4R, and CD44 were the top risk factor target-genes associated with AML survival. An interaction network was constructed that including 607 miRNA-target gene pairs associated with AML survival. Target-genes associated with AML survival were significantly enriched in several pathways including pancreatic secretion, calcium signaling pathway, natural killer cell mediated cytotoxicity, and Alzheimer’s disease. The qRT-PCR results were consistent with our bioinformatics analyses.ConclusionsThe miRNA hsa-mir-425 was identified as the top risk factor miRNA of AML survival and CD44 was identified as one of the top three risk factor target-genes associated with AML survival. Both hsa-mir-425 and CD44 may play key roles in progression and development of AML through calcium signaling pathway and natural killer cell mediated cytotoxicity.

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“…Despite the lack of reports from CRC metabolic steadies, its dysregulation has been described in tumor tissue, peripheral blood, and urine from a variety of cancer-bearing humans and animals including gastric cancer, hepatocellular carcinoma, and myeloid leukemia [ 55 , 56 , 57 ]. This was confirmed in pathway analysis based on gene expression of aggressive breast cancer [ 58 ]. Thus, dysregulation of this pathway may represent a common metabolic profile of advanced cancer.…”

Section: Discussionmentioning

confidence: 72%

Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study

et al. 2020

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Untargeted metabolomics is expected to lead to a better mechanistic understanding of diseases and thus applications of precision medicine and personalized intervention. To further increase metabolite coverage and achieve high accuracy of metabolite quantification, the present proof-of-principle study was to explore the applicability of integration of two-dimensional gas and liquid chromatography-mass spectrometry (GC × GC-MS and 2DLC-MS) platforms to characterizing circulating polar metabolome extracted from plasma collected from 29 individuals with colorectal cancer in comparison with 29 who remained cancer-free. After adjustment of multiple comparisons, 20 metabolites were found to be up-regulated and 8 metabolites were found to be down-regulated, which pointed to the dysregulation in energy metabolism and protein synthesis. While integrating the GC × GC-MS and 2DLC-MS data can dramatically increase the metabolite coverage, this study had a limitation in analyzing the non-polar metabolites. Given the small sample size, these results need to be validated with a larger sample size and with samples collected prior to diagnostic and treatment. Nevertheless, this proof-of-principle study demonstrates the potential applicability of integration of these advanced analytical platforms to improve discrimination between colorectal cancer cases and controls based on metabolite profiles in future studies.

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Analyzing the differentially expressed genes and pathway cross‐talk in aggressive breast cancer

Cited by 22 publications

References 32 publications

Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner

Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner

Identification of miRNA-mRNA Network Associated with Acute Myeloid Leukemia Survival

Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study

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