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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Colon cancer remains a significant global health challenge, necessitating novel therapeutic targets.
• Aldehyde dehydrogenase 1B1 (ALDH1B1) has been identified as a key factor in colon tumor development.
• Tumor heterogeneity and recurrence underscore the need for deeper molecular understanding.

Purpose of the Study:

• To investigate the molecular consequences of ALDH1B1 knockdown in colon cancer cells.
• To identify novel molecular targets for colon cancer therapy by understanding ALDH1B1's role.
• To elucidate the impact of ALDH1B1 on cellular pathways through multi-omics analysis.

Main Methods:

• Utilized a human colon adenocarcinoma cell line (SW480) with ALDH1B1 knockdown (KD) via shRNA.
• Performed integrated multi-omics analysis including transcriptomics, proteomics, and untargeted metabolomics.
• Conducted functional annotation and enrichment analyses on differentially expressed molecules.

Main Results:

• ALDH1B1 KD resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs), and 891 differentially altered metabolites (DAMs).
• DEGs were significantly enriched in integrin-linked kinase (ILK) signaling and growth/development pathways.
• DEPs were primarily associated with apoptosis signaling and cellular stress responses, while DAMs related to biosynthesis and signaling.

Conclusions:

• The study reveals significant molecular alterations in colon cancer cells upon ALDH1B1 suppression.
• Findings highlight ALDH1B1's involvement in critical cellular processes including signaling, stress response, and metabolism.
• This research provides a foundation for future investigations into ALDH1B1 as a potential therapeutic target in colon cancer.