PXD012230

PXD012230 is an original dataset announced via ProteomeXchange.

Title	Integrated multi-omics approach reveals a role of ALDH1A1 in lipid metabolism in human colon cancer cells
Description	An integrated systems approach was used with bioinformatics tools to understand the the role of aldehyde dehydrogenase 1A1 (ALDH1A1) in human colon cancer cells. We combined transcriptomics, proteomics and untargeted metabolomics to gain insight into the mechanisms affected by the suppression of the ALDH1A1 gene in COLO320 cells. RNA-seq and proteomics analyses revealed 1747 transcripts and 336 proteins that were differentially expressed in cells in which the ALDH1A1 had been suppressed by shRNA transfection. Transcriptomics pathway analysis showed significant signaling pathways, such as Wnt/β-catenin (p=3.47E-6), molecular mechanisms of cancer (7.41E-5) and others relevant to lipid metabolism, such as cholesterol biosynthesis I, II and III (p=1.82E-4). Proteomics pathway analysis identified oxidative phosphorylation to be the most highly significant pathway (p=5.01E-31). Pathway analysis of the genes common to the transcriptomics and proteomics analyses revealed the asparagine biosynthesis (p=3.16E-3) and cholesterol biosynthesis the most statistically significant (p=3.36E-3). Univariate analysis of the untargeted metabolomics dataset revealed 859 ions statistically significant. Network analysis showed alterations in pathways linked to energy and lipid metabolism, such carnitine shuttle (p=5.3E-4) and fatty acid oxidation (p=2.9E-2). A systems biology approach was used to integrate all three datasets and a total of 61 pathways were generated. A direct association between the suppression of ALDH1A1 and the Vitamin A (retinol) metabolism pathway and down-regulation of retinol and the UGT2B17, UGT2A3 and PRDX6 genes was shown. In conclusion, the present results confirm the role of ALDH1A1 in retinol metabolism and shows for the first time the influence of this gene on lipid metabolism pathways that may be crucial for cholesterol synthesis in human colon cancer cells. In addition, they demonstrate how an integrated systems approach using unbiased bioinformatics tools can be used to understand the interplay of cellular pathways.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_08:35:56.713.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-03 03:53:10	ID requested
⏵ 1	2021-09-08 08:35:57	announced

Charkoftaki G, Thompson DC, Golla JP, Garcia-Milian R, Lam TT, Engel J, Vasiliou V, Integrated multi-omics approach reveals a role of ALDH1A1 in lipid metabolism in human colon cancer cells. Chem Biol Interact, 304():88-96(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: aldehyde dehydrogenase 1A1

COLO320

transcriptomics

proteomics

metabolomics

colorectal cancer

mass spectrometry

TuKiet Lam
contact affiliation	Yale University; Keck MS & Proteomics Resource
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012230
     1. Label: PRIDE project
     2. Name: Integrated multi-omics approach reveals a role of ALDH1A1 in lipid metabolism in human colon cancer cells