Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; Bioinformatics Support Program, Cushing/Whitney Medical Library, Yale University, New Haven, CT, USA.
Chem Biol Interact. 2023 Oct 1;384:110714. doi: 10.1016/j.cbi.2023.110714. Epub 2023 Sep 15.
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.
结肠癌是全球第三大癌症死亡原因。尽管自 1970 年以来，早期筛查和治疗进展降低了死亡率，但仍需要确定新的治疗靶点，以解决肿瘤异质性和复发问题。先前的工作确定醛脱氢酶 1B1（ALDH1B1）是结肠癌发生的关键因素。为了进一步研究，我们利用人结肠腺癌细胞系（SW480），通过 shRNA 将 ALDH1B1 蛋白表达降低了 80%。通过多组学（转录组学、蛋白质组学和非靶向代谢组学）分析，我们确定了 ALDH1B1 敲低（KD）对结肠癌细胞分子特征的影响。ALDH1B1 表达抑制导致 357 个差异表达基因（DEGs）、191 个差异表达蛋白（DEPs）和 891 个差异代谢物（DAMs）。功能注释和富集分析显示：（1）DEGs 富集在整合素连接激酶（ILK）信号和生长发育途径中；（2）DEPs 主要参与细胞凋亡信号和细胞应激反应途径；（3）DAMs 与生物合成、细胞间和第二信使信号有关。总之，本研究提供了与 ALDH1B1 细胞功能相关的新分子信息，有助于指导未来对结肠癌的研究。
