Gal3st3-KO Mouse

Gal3st3, also known as galactose 3-O-sulfotransferase 3, is an enzyme that acts preferentially on N-acetyllactosamine in N-and O-glycans, playing a critical role in 3'-sulfation of these structures [5]. This sulfation modification may be involved in various biological processes related to glycoprotein functions, such as cell-cell recognition, immune response, and cell-matrix interactions.

In a study on heavy metals and cognitive function, the methylation level at cg18886932, annotated to GAL3ST3, mediated 25.5% of the association between blood arsenic and cognitive function in older adults, suggesting its potential role in arsenic-related cognitive impairment [1]. Another study found that overexpression of Gal3ST3 in cell lines diminished Siglec binding, indicating a new mode of modulating Siglec ligands via sulfation [2]. In ovarian cancer research, GAL3ST3, along with B3GNT7, was identified as required for the formation of the HMOCC-1 antigen, and CHST1 was shown to regulate its abundance [3]. In addition, the expression of Gal3ST3 was detected in the context of lung adenocarcinoma outcomes, being associated with the "dead with disease" outcome [4].

Overall, Gal3ST3 is important for sulfation of N-and O-glycans, which may impact various biological functions. Its role in diseases such as arsenic-associated cognitive impairment, cancer-related antigen formation, and lung adenocarcinoma outcomes, as revealed through these studies, provides valuable insights into the potential mechanisms and possible biomarker development.

References:

1. Wei, Yue, Zhou, Yan-Feng, Xiao, Lili, Zhang, Zhiyong, Yang, Xiaobo. 2024. Associations of Heavy Metals with Cognitive Function: An Epigenome-Wide View of DNA Methylation and Mediation Analysis. In Annals of neurology, 96, 87-98. doi:10.1002/ana.26942. https://pubmed.ncbi.nlm.nih.gov/38661228/

2. Jung, Jaesoo, Enterina, Jhon R, Bui, Duong T, Klassen, John S, Macauley, Matthew S. 2021. Carbohydrate Sulfation As a Mechanism for Fine-Tuning Siglec Ligands. In ACS chemical biology, 16, 2673-2689. doi:10.1021/acschembio.1c00501. https://pubmed.ncbi.nlm.nih.gov/34661385/

3. Shibata, Toshiaki K, Matsumura, Fumiko, Wang, Ping, Aoki, Daisuke, Fukuda, Michiko N. 2011. Identification of mono- and disulfated N-acetyl-lactosaminyl Oligosaccharide structures as epitopes specifically recognized by humanized monoclonal antibody HMOCC-1 raised against ovarian cancer. In The Journal of biological chemistry, 287, 6592-602. doi:10.1074/jbc.M111.305334. https://pubmed.ncbi.nlm.nih.gov/22194598/

4. Deng, Fei, Shen, Lanlan, Wang, He, Zhang, Lanjing. 2020. Classify multicategory outcome in patients with lung adenocarcinoma using clinical, transcriptomic and clinico-transcriptomic data: machine learning versus multinomial models. In American journal of cancer research, 10, 4624-4639. doi:. https://pubmed.ncbi.nlm.nih.gov/33415023/

5. Suzuki, A, Hiraoka, N, Suzuki, M, Hindsgaul, O, Fukuda, M. 2001. Molecular cloning and expression of a novel human beta-Gal-3-O-sulfotransferase that acts preferentially on N-acetyllactosamine in N- and O-glycans. In The Journal of biological chemistry, 276, 24388-95. doi:. https://pubmed.ncbi.nlm.nih.gov/11323440/