Summary of Study ST002959
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001841. The data can be accessed directly via it's Project DOI: 10.21228/M8RB1J This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002959 |
Study Title | Transcriptional regulation of amino acid metabolism by KDM2B |
Study Summary | Epigenetic and metabolic alterations in cancer cells are intertwined. The concentration of metabolites can influence the activity of chromatin modifiers, which in turn can act as metabolic sensors that translate changes in cellular metabolism to transcriptional reprogramming. In the present study, we investigated the role of histone demethylase KDM2B in the metabolic reprogramming of the triple-negative breast cancer (TNBC), in which KDM2B is selectively expressed at high levels. Knockdown of KDM2B in TNBC cell lines reduced their proliferation rate and tumor growth in vivo. Transcriptomic, proteomic, and metabolomic profiling demonstrated that the Serine-Glycine pathway and One Carbon metabolism (SGOC) and other amino acid biosynthetic and catabolic processes are downregulated by the knockdown of KDM2B. Additionally, we see reduction of metabolites produced via these pathways (purines, pyrimidines, formate, glutathione and NADPH). Importantly, the expression of the enzymes involved in the SGOC metabolic pathway (e.g. PHGDH, PSAT1, PSPH, SHMT2, MTHFD1L, MTHFD2 and DHFR) depends on c-MYC, NRF2, and ATF4 which our data show that they are under the positive regulatory control of KDM2B. The epistatic relationship between these factors, with the expression of the enzymes of the SGOC pathway and the effects of the KDM2B knockdown on chromatin occupancy and accessibility of the promoters of these factors is in progress and will be presented. Analysis of TCGA data showed positive and statistically significant correlations between KDM2B and the SGOC gene signature in TNBC patients. In addition, the metabolic pathway signature that distinguishes control and shKDM2B-transduced cells corresponds to the metabolic signature of a subset of TNBCs, which have been reported to carry poor prognosis. The present study highlights the role of the epigenetic factor KDM2B as an upstream regulator of the metabolic reprogramming of TNBC. |
Institute | The Ohio State University |
Last Name | Aldana |
First Name | Julian |
Address | 460 W 12th Ave, Columbus, OH |
aldanaaroca.1@osu.edu | |
Phone | 6142180748 |
Submit Date | 2023-10-23 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2023-11-17 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN004859 | AN004860 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | Reversed phase | Reversed phase |
Chromatography system | Agilent 1290 Infinity | Agilent 1290 Infinity |
Column | Agilent InfityLab Poroshell 120 SB-C18 (100 x 2.1mm, 2.7um) | Agilent InfityLab Poroshell 120 SB-C18 (100 x 2.1mm, 2.7um) |
MS Type | ESI | ESI |
MS instrument type | QTOF | QTOF |
MS instrument name | Agilent 6545 QTOF | Agilent 6545 QTOF |
Ion Mode | POSITIVE | NEGATIVE |
Units | Relative intensity | Relative intensity |
MS:
MS ID: | MS004603 |
Analysis ID: | AN004859 |
Instrument Name: | Agilent 6545 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
MS Comments: | ESI configuration included a mass range from 100 to 1,200 m/z, full scan mode at a scan rate of 2 scans per second, 3000V of capillary, 10 L/min of nebulizer gas flow and 300 °C of gas temperature. MS/MS data were collected in data dependent acquisition (DDA) mode with a scan rate of 5 spectra/sec and dynamic exclusion of 30 seconds for precursor ion selection and fragmentation, using 10 to 30 V. |
Ion Mode: | POSITIVE |
MS ID: | MS004604 |
Analysis ID: | AN004860 |
Instrument Name: | Agilent 6545 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
MS Comments: | ESI configuration included a mass range from 100 to 1,200 m/z, full scan mode at a scan rate of 2 scans per second, 3000V of capillary, 10 L/min of nebulizer gas flow and 300 °C of gas temperature. MS/MS data were collected in data dependent acquisition (DDA) mode with a scan rate of 5 spectra/sec and dynamic exclusion of 30 seconds for precursor ion selection and fragmentation, using 10 to 30 V. |
Ion Mode: | NEGATIVE |