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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Project:

Project ID:	PR001947
Project DOI:	doi: 10.21228/M82431
Project Title:	Targeting SOX13 inhibits the assembly of respiratory chain supercomplexes to overcome ferroptosis-resistance in gastric cancer
Project Type:	Untargeted metabolomic analysis
Project 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
Department:	Department of Gastric Surgery
Last Name:	Mingzhe
First Name:	Ma
Address:	building 18, 29 nong linling road, xuhui district, shanghai, 200024, China
Email:	mmz666@163.com, ding@bioinformatics.com.cn
Phone:	13917006049

Subject:

Subject ID:	SU003251
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Species Group:	Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Sample source	transfected
SA339330	NC-1	Erastin-resis SNU-668 cells	shRNA-NC
SA339331	Sox13-11	Erastin-resis SNU-668 cells	shRNA-SOX23
SA339332	NC-2	Erastin-resis SNU-669 cells	shRNA-NC
SA339333	Sox13-12	Erastin-resis SNU-669 cells	shRNA-SOX24
SA339334	NC-3	Erastin-resis SNU-670 cells	shRNA-NC
SA339335	NC-4	Erastin-resis SNU-671 cells	shRNA-NC
SA339336	NC-5	Erastin-resis SNU-672 cells	shRNA-NC
SA339337	NC-6	Erastin-resis SNU-673 cells	shRNA-NC
SA339338	NC-7	Erastin-resis SNU-674 cells	shRNA-NC
SA339339	NC-8	Erastin-resis SNU-675 cells	shRNA-NC
SA339340	NC-9	Erastin-resis SNU-676 cells	shRNA-NC
SA339341	NC-10	Erastin-resis SNU-677 cells	shRNA-NC
SA339342	NC-11	Erastin-resis SNU-678 cells	shRNA-NC
SA339343	NC-12	Erastin-resis SNU-679 cells	shRNA-NC
SA339344	Sox13-1	Erastin-resis SNU-680 cells	shRNA-SOX13
SA339345	Sox13-2	Erastin-resis SNU-681 cells	shRNA-SOX14
SA339346	Sox13-3	Erastin-resis SNU-682 cells	shRNA-SOX15
SA339347	Sox13-4	Erastin-resis SNU-683 cells	shRNA-SOX16
SA339348	Sox13-5	Erastin-resis SNU-684 cells	shRNA-SOX17
SA339349	Sox13-6	Erastin-resis SNU-685 cells	shRNA-SOX18
SA339350	Sox13-7	Erastin-resis SNU-686 cells	shRNA-SOX19
SA339351	Sox13-8	Erastin-resis SNU-687 cells	shRNA-SOX20
SA339352	Sox13-9	Erastin-resis SNU-688 cells	shRNA-SOX21
SA339353	Sox13-10	Erastin-resis SNU-689 cells	shRNA-SOX22

Showing results 1 to 24 of 24

Showing results 1 to 24 of 24

Collection:

Collection ID:	CO003244
Collection Summary:	SNU-668 Erastin-resistant cells were were cultured for 48-72 h in advanced RPMI-1640 medium (Gibco) without supplements.
Sample Type:	SNU-668 Erastin-resistant cells

Treatment:

Treatment ID:	TR003260
Treatment Summary:	Erastin-resis SNU-668 cells transfected with shRNA-NC or shRNA-SOX13

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.

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

Analysis:

Analysis ID:	AN005144
Analysis Type:	MS
Analysis Protocol File:	FUSCC_methods.pdf
Chromatography ID:	CH003894
Has Mz:	1
Rt Units:	No RT data
Results File:	ST003134_AN005144_Results.txt
Units:	m/z