Summary of Study ST003569
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.
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| Study ID | ST003569 |
| Study Title | Differentially regulated metabolites in colorectal cancer from Rosa26Hmga1/+ and Hmga1IEC-OE/+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 firstly. The results showed that fatty acyl metabolites were mainly down-regulated in HMGA1-deficient IECs. Further, untargeted metabolomics analysis on tumors derived from the Hmga1IEC-OE/+ mice also showed that fatty acyl metabolites were mainly up-regulated by HMGA1 overexpression. FA is a major component of structurally complex lipids and is one of the most basic categories of bio-lipids. We analyzed all lipids-related metabolites and found the free fatty acids were significantly up-regulated in tumors derived from the Hmga1IEC-OE/+ mice. Thus, untargeted metabolomics measurement of IECs (CRCs) from both Hmga1 conditional knockout (Hmga1△IEC) and knock-in (Hmga1IEC-OE/+) mice demonstrates a positive correlation between expression of HMGA1 and activation of fatty acid synthesis. |
| 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) | mzML |
| 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: | SU003698 |
| 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 | Sample source | Genotype |
|---|---|---|---|
| SA389597 | T23320685a | Colorectum tissue | HMGA1-knockin |
| SA389598 | T23320688a | Colorectum tissue | HMGA1-knockin |
| SA389599 | T23320691a | Colorectum tissue | HMGA1-knockin |
| SA389600 | T23320676a | Colorectum tissue | Wild-type |
| SA389601 | T23320679a | Colorectum tissue | Wild-type |
| SA389602 | T23320682a | Colorectum tissue | Wild-type |
| Showing results 1 to 6 of 6 |
Collection:
| Collection ID: | CO003691 |
| Collection Summary: | The C57BL/6J mice were selected for the induction of CRC using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice received an intraperitoneal injection of AOM (Sigma-Aldrich, St. Louis, MO, USA) at 10 mg/kg body weight. One week later, they were given 2% (w/v) DSS (Meilunbio, Dalian, China) in drinking water for 5 days, followed by regular water for 14 days. This sequence, termed a DSS cycle, was repeated three times. Body weight and stool were continuously monitored until euthanasia at week 12. Since orthotopic colorectal tumors induced by AOM/DSS were not directly visible during the mice's lifetime, we determined the timing of sacrifice based on weight loss and behavioral observations. Mice were euthanized when they lost 20% of their pre-experiment body weight, showed signs of severe debilitation, or were on the verge of death, such as being unable to move, and/or body condition scoring (BCS) reached 2.0. Distal colon tissues were collected, and visible tumors on the colorectal mucosa were counted. The samples was saved at -80℃ condition. |
| Sample Type: | Colorectum |
Treatment:
| Treatment ID: | TR003707 |
| Treatment Summary: | The samples were not subjected to any further treatment. |
Sample Preparation:
| Sampleprep ID: | SP003705 |
| Sampleprep Summary: | The sample was thawed on ice and homogenized by a grinder (30 HZ) for 20 s. A 400 μL solution (Methanol: Water = 7:3, V/V) containing internal standard was added in to 20 mg ground sample, and shaken at 1500 rpm for 5 min. After placing on ice for 15 min, the sample was centrifuged at 12000 rpm for 10 min (4 °C). A 300 μL of supernatant was collected and placed in -20 °C for 30 min. The sample was then centrifuged at 12000 rpm for 3 min (4 °C). A 200 μL aliquots of supernatant were transferred for LC-MS analysis. |
Combined analysis:
| Analysis ID | AN005863 | AN005864 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Shimadzu Nexera LC-30A | Shimadzu Nexera LC-30A |
| Column | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| MS Type | ESI | ESI |
| MS instrument type | Triple TOF | Triple TOF |
| MS instrument name | ABI Sciex 6600 TripleTOF | ABI Sciex 6600 TripleTOF |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
Chromatography:
| Chromatography ID: | CH004453 |
| 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 |
MS:
| MS ID: | MS005583 |
| Analysis ID: | AN005863 |
| Instrument Name: | ABI Sciex 6600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | The data acquisition was operated using the information-dependent acquisition (IDA) mode using Analyst TF 1.7.1 Software (Sciex, Concord, ON, Canada). The source parameters were set as follows: ion source gas 1 (GAS1),50 psi; ion source gas 2 (GAS2), 50 psi; curtain gas (CUR), 25 psi; temperature(TEM), 550 °C; declustering potential (DP), 60 V, or−60 V in positive or negative modes, respectively; and ion spray voltagefloating (ISVF), 5000 V or−4000 V in positive or negative modes, respectively. The TOF MS scan parameters were set as follows: mass range, 50–1000 Da; accumulation time, 200 ms; and dynamic background subtract, on. The product ion scan parameters were set as follows: mass range, 25–1000 Da; accumulation time, 40 ms; collision energy, 30 or−30 V in positive or negative modes, respectively; collision energy spread, 15; resolution, UNIT; charge state, 1 to 1; intensity, 100 cps; exclude isotopes within 4 Da; mass tolerance, 50 ppm; maximum number of candidate ions to monitor per cycle, 18. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005584 |
| Analysis ID: | AN005864 |
| Instrument Name: | ABI Sciex 6600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | The data acquisition was operated using the information-dependent acquisition (IDA) mode using Analyst TF 1.7.1 Software (Sciex, Concord, ON, Canada). The source parameters were set as follows: ion source gas 1 (GAS1),50 psi; ion source gas 2 (GAS2), 50 psi; curtain gas (CUR), 25 psi; temperature(TEM), 550 °C; declustering potential (DP), 60 V, or−60 V in positive or negative modes, respectively; and ion spray voltagefloating (ISVF), 5000 V or−4000 V in positive or negative modes, respectively. The TOF MS scan parameters were set as follows: mass range, 50–1000 Da; accumulation time, 200 ms; and dynamic background subtract, on. The product ion scan parameters were set as follows: mass range, 25–1000 Da; accumulation time, 40 ms; collision energy, 30 or−30 V in positive or negative modes, respectively; collision energy spread, 15; resolution, UNIT; charge state, 1 to 1; intensity, 100 cps; exclude isotopes within 4 Da; mass tolerance, 50 ppm; maximum number of candidate ions to monitor per cycle, 18. |
| Ion Mode: | NEGATIVE |
