Summary of Study ST003134

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 PR001947. The data can be accessed directly via it's Project DOI: 10.21228/M82431 This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST003134
Study TitleTargeting SOX13 inhibits the assembly of respiratory chain supercomplexes to overcome ferroptosis-resistance in gastric cancer
Study SummaryTherapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential. We conducted untargeted metabolomic analysis of Erastin-resis SNU-668 cells transfected with shRNA-SOX13 or shRNA-NC.
Institute
Fudan University Shanghai Cancer Center
Last NameMa
First NameMingzhe
Addresslingling road, xuhui district, shanghai, China
Emailmmz666@163.com, ding@bioinformatics.com.cn
Phone13917006049
Submit Date2024-03-20
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-04-12
Release Version1
Mingzhe Ma Mingzhe Ma
https://dx.doi.org/10.21228/M82431
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005144
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1260
Column Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units m/z

Chromatography:

Chromatography ID:CH003894
Chromatography Summary:Samples were separated on an amide column, using mobile phase A consists of water mixed with 25 mM ammonium acetate and 25 mM Ammonium hydroxide and mobile phase B ACN. The injection volume was 4 µL and flow rate was 0.4 ml/min. 1. The generic HPLC gradient was listed in Table 1: 2.
Methods Filename:FUSCC_methods.pdf
Instrument Name:Agilent 1260
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
Column Temperature:350
Flow Gradient:0.0 min 10% A; 1.0 min 10% A; 11.0 min 13% A; 14.0 min 20% A; 16.5 min 30% A; 18.5 min 50% A; 20.5 min 80% A; 25.0 min 80% A; 25.1 min 10% A; 34.0 min 10% A
Flow Rate:0.4 ml/min
Solvent A:100% water; 25mM ammonium acetate; 25mM ammonium hydroxide
Solvent B:100% acetonitrile
Chromatography Type:Reversed phase
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