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Glucosaminyl (N-acetyl) transferase 3, mucin type (GCNT3) mRNA is the transcript encoding a key enzyme in the O-glycan biosynthesis pathway. This enzyme, also known as C2GnT-M, is responsible for the formation of core 2 and core 4 O-glycan branches, as well as I-branches, which are critical for the synthesis of mucins and the glycosylation of various cell surface proteins (UniProtKB: O95395). GCNT3 mRNA expression is highly regulated and often dysregulated in human malignancies; it is significantly overexpressed in pancreatic, lung, and breast cancers, where it promotes tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) (PubMed: 26879471, 35867813). Conversely, its expression is frequently downregulated in colorectal cancer, where it may act as a tumor suppressor (PubMed: 18024424). Therapeutic targeting of GCNT3 mRNA, primarily through RNA interference (siRNA/shRNA) or microRNA-mediated silencing, aims to disrupt the aberrant glycosylation patterns that facilitate cancer progression and immune evasion (PubMed: 29855486). Additionally, small molecules like talniflumate have been identified to inhibit GCNT3 activity and reduce its expression levels, offering a potential strategy to overcome chemoresistance and improve patient outcomes in mucin-producing tumors (PubMed: 26879471).
RNA interference (siRNA/shRNA), small molecule inhibition of enzyme activity and expression, and microRNA-mediated gene silencing.
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