Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells

• Published in: Chemico-biological interactions Vol. 384; p. 110714
• Main Authors: Wang, Yewei, Popovic, Zeljka, Charkoftaki, Georgia, Garcia-Milian, Rolando, Lam, TuKiet T., Thompson, David C., Chen, Ying, Vasiliou, Vasilis
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.10.2023
• Subjects: Adenocarcinoma; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase - metabolism; Aldehyde Dehydrogenase 1 Family - metabolism; Aldehyde Dehydrogenase, Mitochondrial - genetics; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Humans; Mass spectrometry; Metabolomics; Multiomics; Proteomics; RNASeq; Metabolomics; Colon cancer; Mass spectrometry; RNASeq; Proteomics
• ISSN: 0009-2797; 1872-7786; 1872-7786
• DOI: 10.1016/j.cbi.2023.110714

Colon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of ALDH1B1 knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer. [Display omitted] •Suppression of ALDH1B1 in SW480 cells resulted in 357 DEGs, 191 DEPs and 891 DAMs.•DEGs were enriched in pathways of ILK signaling and growth and development.•DEPs were enriched in pathways of apoptosis signaling and cellular stress response.•DAMs were associated with biosynthesis, intercellular and second messenger signaling.