Summary of Study ST002910
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 PR001810. The data can be accessed directly via it's Project DOI: 10.21228/M8RD98 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 | ST002910 |
| Study Title | Identifying the impact of RelA overexpression in triple negative breast cancer cells using mass spectroscopy-based proteomics and metabolomics analysis |
| Study Type | LC/MS/MS |
| Study Summary | Introduction: The incidence of chemotherapeutic resistance among breast cancer patients continues to rise steadily. The expression of RelA, a prominent member of the Rel family, is closely associated with the aggressiveness of triple-negative breast cancer (TNBC) and a poor prognosis for patients. Consequently, it is crucial to deeply investigate the molecular changes that underlie breast cancer progression and chemotherapy resistance associated with RelA overexpression. Materials and Methods: In this study, we performed a comprehensive quantitative analysis of proteomics and metabolomics in triple negative breast cancer (TNBC) cells overexpressing RelA, compared to TNBC cells with basal levels. State-of-the-art Trapped Ion Mobility Spectroscopy, Time-of-Flight Mass Spectrometry (TIMS-TOF-MS) was employed to achieve high-resolution analysis. Results: The results unveiled 27 significantly dysregulated proteins and 21 altered metabolites in MDA-MB-231 RelA cells relative to MDA-MB-231 cells. The upregulated proteins in MDA-MB-231 RelA cells include interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and cytochrome b5, which are involved in tumor migration and progression and regulation of the cellular redox system, respectively. Conversely, the adhesion molecule, integrin alpha-2, was downregulated in MDA-MB-231 RelA cells. In addition, metabolomics analysis revealed significant upregulation in the signal transducer, cyclic AMP, and downregulation in multiple nucleotides such as pyridine, adenine, and thymidine. The integrated analysis of multi-omics data highlighted the highest impacted pathways, including ABC transporters, arginine biosynthesis, purine, pyruvate, pyrimidine, glutathione, and phenylalanine metabolism. Conclusion: This study effectively recognized significantly dysregulated proteins and metabolites in MDA-MB-231 RelA cells, providing valuable insights into potential proteins, metabolites, and signaling pathways that mediate the aggressiveness of TNBC through RelA. Moreover, the multi-omics integrated analysis elucidated RelA role in chemotherapy resistance, tumor progression, migration, and invasion, which would propose potential biomarkers and novel therapeutic targets. |
| Institute | Sharjah Institute for Medical Research |
| Last Name | Facility |
| First Name | Core |
| Address | M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates |
| tims-tof@sharjah.ac.ae | |
| Phone | +971 6 5057656 |
| Submit Date | 2023-09-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-05 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004779 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Bruker Elute |
| Column | Hamilton Intensity Solo 2 C18 (100 mm x 2.1 mm, 1.8um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Bruker timsTOF |
| Ion Mode | POSITIVE |
| Units | AU |
MS:
| MS ID: | MS004525 |
| Analysis ID: | AN004779 |
| Instrument Name: | Bruker timsTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | Using an Apollo II electrospray ionization (ESI) source or an CaptiveSpray ion source, and a timsTOF (Bruker, Bremen, Germany), the MS analysis was carried out. For metabolomics, the nebulizer pressure was adjusted to 2.2 bar, the drying temperature to 220°C, and the gas flow rate to 10 L/min. 4500 V was the capillary voltage, while 500 V was the end plate offset and the scan range for metabolomics was 20-1300 m/z. The instrument was operated in auto-MS/MS mode and the acquisition was performed using the positive mode at 12 Hz. The width of the precursor ion was ±0.5, the cycle time was 0.5 sec., and the threshold was 400 counts per thousand. Active exclusion was excluded after 3 spectra and released after 0.2 min. For MS2 acquisition the data dependent acquisition (DDA) was used, and the collision energy stepping fluctuated between 100 and 250% set at 20 eV. In the first 0.3 minutes of each LC-MS/MS run, sodium formate was injected as an external calibrant during data processing |
| Ion Mode: | POSITIVE |
