St8sia4, also known as α -2,8 -sialyltransferase 4, is an enzyme involved in the synthesis of polysialic acid (polySia), which can modify proteins like neural cell adhesion molecule (NCAM) [4,9]. It is part of a developmental program associated with germ layer formation from human pluripotent stem cells, where it contributes to lineage-specific polysialylation [4].

In disease-related research, St8sia4 has been identified as a common diagnostic marker for atherosclerosis and ankylosing spondylitis, being upregulated in samples from both diseases, and is associated with the immune microenvironment [1]. In breast cancer, the lncRNA MALAT1/miR-26a/26b/ST8SIA4 axis mediates cell invasion and migration, and ST8SIA4 is upregulated in tumor tissues and highly metastatic cell lines, with its knockdown inhibiting malignant behaviors [2,6]. In cholangiocarcinoma, miR-144-5p and miR-451a inhibit cell growth by decreasing ST8SIA4 expression [5]. In chronic myelocytic leukemia, miR-181c inhibits chemoresistance by targeting ST8SIA4 [7]. Also, in lung cancer, lnc-ST8SIA4-12 (a related lncRNA) is upregulated and may serve as a biomarker for diagnosis and progression prediction [8]. In BRCA1 -mutant breast cancers, ST8SIA4 -mediated hypersialylation generates an acidic and immunosuppressive microenvironment, promoting metastasis and immunotherapy resistance [3].

In conclusion, St8sia4 plays significant roles in both normal development and multiple disease conditions. Its involvement in diseases such as atherosclerosis, ankylosing spondylitis, breast cancer, cholangiocarcinoma, chronic myelocytic leukemia, and lung cancer highlights its potential as a diagnostic biomarker and therapeutic target. The study of St8sia4 in these contexts helps in understanding disease mechanisms and developing new treatment strategies.