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.

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.

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Study ID	ST003134
Study Title	Targeting SOX13 inhibits the assembly of respiratory chain supercomplexes to overcome ferroptosis-resistance in gastric cancer
Study Summary	Therapeutic 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 Name	Ma
First Name	Mingzhe
Address	lingling road, xuhui district, shanghai, China
Email	mmz666@163.com, ding@bioinformatics.com.cn
Phone	13917006049
Submit Date	2024-03-20
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2024-04-12
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP003258
Sampleprep Summary:	For untargeted metabolomics, a total of 24 samples were analyzed (n=12 Erastinresis SNU-668 cells transfected with shRNA-NC, n=12 Erastinresis SNU-668 cells transfected with shRNA-SOX13). 2 × 105 cells of adherent cells were harvested in six-well plates. When collected, cells were washed by cold PBS buffer twice and immediately quenched in liquid nitrogen. Tumor samples were weighed and pulverized. All samples were lysed in 1 ml of −80°C extraction solvent (80% methanol/water). After centrifugation (20,000g, 4°C, 15 min), supernatant was transferred to a new tube, and samples were dried using a vacuum centrifugal concentrator. Blood samples from patients and mice were collected into BD Vacutainer blood collection tubes and placed on ice. Serum was isolated by centrifugation (15,000g, 4°C, 10 min), and aliquots of 100 μl of supernatant were frozen immediately at −80°C. Metabolites were reconstituted in 150 μl of 80% acetonitrile/water, vortexed, and centrifuged to remove insoluble material. All samples were stored at −80°C before LC-MS/MS analysis.

Sampleprep ID:

SP003258

Sampleprep Summary:

For untargeted metabolomics, a total of 24 samples were analyzed (n=12 Erastinresis SNU-668 cells transfected with shRNA-NC, n=12 Erastinresis SNU-668 cells transfected with shRNA-SOX13). 2 × 105 cells of adherent cells were harvested in six-well plates. When collected, cells were washed by cold PBS buffer twice and immediately quenched in liquid nitrogen. Tumor samples were weighed and pulverized. All samples were lysed in 1 ml of −80°C extraction solvent (80% methanol/water). After centrifugation (20,000g, 4°C, 15 min), supernatant was transferred to a new tube, and samples were dried using a vacuum centrifugal concentrator. Blood samples from patients and mice were collected into BD Vacutainer blood collection tubes and placed on ice. Serum was isolated by centrifugation (15,000g, 4°C, 10 min), and aliquots of 100 μl of supernatant were frozen immediately at −80°C. Metabolites were reconstituted in 150 μl of 80% acetonitrile/water, vortexed, and centrifuged to remove insoluble material. All samples were stored at −80°C before LC-MS/MS analysis.