Summary of Study ST003568
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 PR002202. The data can be accessed directly via it's Project DOI: 10.21228/M80G0Q 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 | ST003568 |
| Study Title | Differentially regulated metabolites in intestinal epithelial cells from Hmga1flox/flox and Hmga1△IEC mice |
| Study Summary | Dysregulations of cell metabolism, such as elevated aerobic glycolysis and increased fatty acid metabolism, play a critical role in the tumorigenesis of colorectal cancer (CRC). To determine whether HMGA1 promotes CRC through regulating cell metabolism, we performed an untargeted metabolomics using intestinal epithelial cells (IECs) from Hmga1flox/flox and Hmga1△IEC mice. In comparison with the Hmga1flox/flox mice, the Hmga1△IEC mice displayed 187 up-regulated metabolites and 120 down-regulated metabolites in IECs. Enrichment analysis of the metabolites showed that these differential metabolites mainly enriched in 20 pathways. Fatty acid synthesis was the most significantly deregulated signal pathway in HMGA1 deficient IECs. We separated the altered metabolites into up-regulated and down-regulated groups, and showed the top five classes of metabolites in up-regulated and down-regulated groups in heatmaps. The results showed that fatty acyl metabolites were mainly down-regulated in HMGA1-deficient IECs. |
| Institute | Henan University |
| Last Name | Xu |
| First Name | Zhi-Xiang |
| Address | Jinming Road, Kaifeng, Henan province, 475000, China |
| zhixiangxu08@gmail.com | |
| Phone | 86-13270538760 |
| Submit Date | 2024-11-04 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-12-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002202 |
| Project DOI: | doi: 10.21228/M80G0Q |
| Project Title: | High mobility group A1 (HMGA1) promotes the tumorigenesis of colorectal cancer by increasing lipid synthesis |
| Project Type: | LC-MS |
| Project Summary: | Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the high energy and biosynthetic demands required for their proliferation. High mobility group A1 (HMGA1) is a structural transcription factor and frequently overexpressed in human colorectal cancer (CRC). Here, we show that HMGA1 promotes CRC progression by driving lipid synthesis in a AOM/DSS-induced CRC mouse model. Using conditional knockout (Hmga1△IEC) and knock-in (Hmga1IEC-OE/+) mouse models, we demonstrate that HMGA1 enhances CRC cell proliferation and accelerates tumor development by upregulating fatty acid synthase (FASN). Mechanistically, HMGA1 increases the transcriptional activity of sterol regulatory element-binding protein 1 (SREBP1) on the FASN promoter, leading to increased lipid accumulation in intestinal epithelial cells. Moreover, a high-fat diet exacerbates CRC progression in Hmga1△IEC mice, while pharmacological inhibition of FASN by orlistat reduces tumor growth in Hmga1IEC-OE/+ mice. Our findings suggest that targeting lipid metabolism could offer a promising therapeutic strategy for CRC. |
| Institute: | Henan University |
| Last Name: | Xu |
| First Name: | Zhi-Xiang |
| Address: | Jinming Road, Kaifeng, Henan province, 475000, China |
| Email: | zhixiangxu08@gmail.com |
| Phone: | 86-13270538760 |
Subject:
| Subject ID: | SU003697 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA389591 | T2318027a | HMGA1-knockout |
| SA389592 | T2318028a | HMGA1-knockout |
| SA389593 | T2318029a | HMGA1-knockout |
| SA389594 | T2318024a | Wild-type |
| SA389595 | T2318025a | Wild-type |
| SA389596 | T2318026a | Wild-type |
| Showing results 1 to 6 of 6 |
Collection:
| Collection ID: | CO003690 |
| Collection Summary: | The mice were euthanized, washed with pre-cooled PBS, and dissected longitudinally. Colon tissues of the mice were isolated and cut into 0.5 - 1.0 cm fragments and flushed 15 - 20 times with pre-cooled PBS followed by incubation in 20 mL HBSS containing 2% fetal bovine serum, 1 mM EDTA, and 1mM dithiothreitol (DTT) in a 50 mL centrifugal tube with constant shaking at 200 rpm for 20 min at 37 °C. The washed colon tissue pieces were transferred into a new tube containing 20 mL HBSS buffer and incubated for another 20 min. The colon tissues were cleaned again with 5 mL DMEM medium containing 10% FBS and then transfered to a tube with 5 mL DMEM containing 10% FBS, 50 U/mL collagenase type VIII, and 50 U/mL DNase I, and incubated at 37 °C for 50 min with constant shaking at 200 rpm. The digested tissue fragments were swirled for 30s and the undigested tissue was removed through a 40μm filter. The filtered cell suspension was centrifugated at 410 x g for 5 min at 4°C and then re-suspended in 10 mL DMEM containing 15% FBS, 100 U/mL penicillin and 100 μg/mL streptomycin (Thermo Fisher Scientific) for further culture. |
| Sample Type: | intestinal epithelial cells |
Treatment:
| Treatment ID: | TR003706 |
| Treatment Summary: | The samples were not subjected to any further treatment. |
Sample Preparation:
| Sampleprep ID: | SP003704 |
| Sampleprep Summary: | Take out the sample from the -80 °C refrigerator and thaw it on ice. Add 1mL of the extraction solvent (MTBE: MeOH =3:1, v/v) containing internal standard mixture. After whirling the mixture for 15 min, 200 μL of water was added. Vortex for 1 min and centrifuge at 12,000 rpm for 10 min. 200 μL of the upper organic layer was collected and evaporated using a vacuum concentrator. The dry extract was dissolved in 200 μL reconstituted solution (ACN: IPA=1:1, v/v) to LC-MS/MS analysis. |
Chromatography:
| Chromatography ID: | CH004452 |
| Instrument Name: | Shimadzu Nexera LC-30A |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| Column Temperature: | 40 °C |
| Flow Gradient: | (A:B) - 95:5, V/V at 0 min, 80:20 V/V at 2.0 min, 40:60 V/V at 5 min, 1:99 V/V at 6 min, 1:99 V/V at 7.5 min, 95: 5 V/V at 7.6 min, 95: 5 V/V at 10 min |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | 100% water; 0.1 % formic acid |
| Solvent B: | 100% acetonitrile; 0.1 % formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN005861 |
| Analysis Type: | MS |
| Chromatography ID: | CH004452 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003568_AN005861_Results.txt |
| Units: | Peak area |
| Analysis ID: | AN005862 |
| Analysis Type: | MS |
| Chromatography ID: | CH004452 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003568_AN005862_Results.txt |
| Units: | Peak area |
