St3gal3, also known as β-galactoside-α2,3-sialyltransferase III, is a key enzyme responsible for sialyl Lewis X (sLeX) oligosaccharide biosynthesis. It is involved in α2,3-sialylation of N-glycans and may regulate cell biological functions through modifying characteristic target proteins. It also plays a role in the sialylation process which is associated with multiple biological pathways and has importance in various biological processes [6,8].

Pathogenic mutations in the ST3GAL3 gene lead to an autosomal recessive disorder. Patients with ST3GAL3-related developmental and epileptic encephalopathy (DEE-15) present with intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Seizures often occur in infancy, possibly as epileptic spasms, and may show good response to treatment. Some patients also exhibit tremors. ST3GAL3 deficiency has also been associated with repetitive behavior [1,2,7]. In ovarian cancer, elevated St3gal3 is linked to poor prognosis. St3gal3 knockdown in immunocompetent mice inhibits tumor growth, enhances accumulation of functional CD8+ T cells, and repolarizes tumor-associated macrophages. It also confers paclitaxel-mediated chemoresistance in ovarian cancer cells by attenuating caspase-8/3 signaling. In rheumatoid arthritis, ST3GAL3 promotes the inflammatory response of fibroblast-like synoviocytes by activating the TLR9/MyD88 pathway [3,4,5].

In conclusion, St3gal3 is crucial for sialylation-related biological functions. Studies on ST3GAL3-related gene mutations in patients help understand its role in neurodevelopmental disorders like DEE-15. Research on its role in cancer and rheumatoid arthritis provides insights into disease mechanisms, suggesting St3gal3 as a potential therapeutic target in these disease areas. [1-5,8]

References:

1. Whitney, Robyn, Jain, Puneet, RamachandranNair, Rajesh, Tarnopolsky, Mark, Meaney, Brandon. 2023. The epilepsy phenotype of ST3GAL3-related developmental and epileptic encephalopathy. In Epilepsia open, 8, 623-632. doi:10.1002/epi4.12747. https://pubmed.ncbi.nlm.nih.gov/37067065/

2. Khamirani, Hossein Jafari, Zoghi, Sina, Faghihi, Fatemeh, Ehsani, Elham, Dianatpour, Mehdi. 2021. Phenotype of ST3GAL3 deficient patients: A case and review of the literature. In European journal of medical genetics, 64, 104250. doi:10.1016/j.ejmg.2021.104250. https://pubmed.ncbi.nlm.nih.gov/34022416/

3. Cao, Kankan, Zhang, Guodong, Yang, Moran, Lu, Jiaqi, Liu, Haiou. . Attenuation of Sialylation Augments Antitumor Immunity and Improves Response to Immunotherapy in Ovarian Cancer. In Cancer research, 83, 2171-2186. doi:10.1158/0008-5472.CAN-22-3260. https://pubmed.ncbi.nlm.nih.gov/37172314/

4. Zhang, Xian, Yang, Xinying, Chen, Ming, Lin, Shaoqiang, Wang, Xiaoyu. 2019. ST3Gal3 confers paclitaxel‑mediated chemoresistance in ovarian cancer cells by attenuating caspase‑8/3 signaling. In Molecular medicine reports, 20, 4499-4506. doi:10.3892/mmr.2019.10712. https://pubmed.ncbi.nlm.nih.gov/31702036/

5. Xu, Liming, Niu, Xuegang, Liu, Yifan, Liu, Lining. 2022. ST3GAL3 Promotes the Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis by Activating the TLR9/MyD88 Pathway. In Mediators of inflammation, 2022, 4258742. doi:10.1155/2022/4258742. https://pubmed.ncbi.nlm.nih.gov/36405992/

6. Qi, Feng, Isaji, Tomoya, Duan, Chengwei, Fukuda, Tomohiko, Gu, Jianguo. 2019. ST3GAL3, ST3GAL4, and ST3GAL6 differ in their regulation of biological functions via the specificities for the α2,3-sialylation of target proteins. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34, 881-897. doi:10.1096/fj.201901793R. https://pubmed.ncbi.nlm.nih.gov/31914669/

7. Hu, Jihong, Liu, Juan, Guo, Chunguang, Tan, Yaqiong, Pan, Ying. 2023. Clinical report and genetic analysis of a Chinese patient with developmental and epileptic encephalopathy associated with novel biallelic variants in the ST3GAL3 gene. In Molecular genetics & genomic medicine, 12, e2322. doi:10.1002/mgg3.2322. https://pubmed.ncbi.nlm.nih.gov/37938134/

8. Yu, Ming, Wang, Hao, Liu, Jianwei, Liu, Shuai, Yan, Qiu. 2018. The sialyltransferase ST3Gal3 facilitates the receptivity of the uterine endometrium in vitro and in vivo. In FEBS letters, 592, 3696-3707. doi:10.1002/1873-3468.13252. https://pubmed.ncbi.nlm.nih.gov/30220088/