Abstract
BackgroundGlycosyltransferases play a crucial role in various cancers. β1, 3-N-acetylglucosaminyltransferase 2, a polylactosamine synthase, is an important member of the glycosyltransferase family. However, the biological function and regulatory mechanism of β3GNT2 in esophageal carcinoma (ESCA) is still poorly understood.MethodsThe Cancer Genome Atlas and Genotype-Tissue Expression databases were used for gene expression and prognosis analysis. Quantitative real-time PCR, Western blot, and immunohistochemistry were performed to detect the expression of β3GNT2 in ESCA cell lines and tissues. In vitro assays and xenograft tumor models were utilized to evaluate the impact of β3GNT2 on ESCA progression. The downstream effectors and upstream regulators of β3GNT2 were predicted by online software and verified by functional experiments.ResultsWe found that β3GNT2 was highly expressed in ESCA tissues and positively correlated with poor prognosis in ESCA patients. β3GNT2 expression was closely associated with the tumor size, TNM stage, and overall survival of ESCA patients. Functionally, β3GNT2 promoted ESCA cell growth, migration, and invasion in vitro, as well as tumorigenesis in vivo. Mechanistically, β3GNT2 knockdown decreased the expression of the polylactosamine on EGFR. Knockdown of β3GNT2 also inhibited the JAK/STAT signaling pathway. Meanwhile, the JAK/STAT inhibitor could partly reverse the biological effects caused by β3GNT2 overexpression. Moreover, β3GNT2 expression was positively regulated by CREB1 and negatively regulated by miR-133b. Both CREB1 and miR-133b was involved in the β3GNT2-mediated ESCA progression.ConclusionsOur study, for the first time, reveals the importance of β3GNT2 in ESCA progression and offers a potential therapeutic target for ESCA.
Highlights
Glycosyltransferases play a crucial role in various cancers. β1, 3-N-acetylglucosaminyltransferase 2, a polylactosamine synthase, is an important member of the glycosyltransferase family
We further investigated the relationship between glycosyltransferases and the overall survival of esophageal carcinoma (ESCA) patients
Kaplan–Meier analysis showed that only five glycosyltransferases, including β3GNT2, ST3GAL4, β4GALT2, PIGA, and GYG1 were related to overall survival (Fig. 1D, Additional file 1: Table S1)
Summary
Glycosyltransferases play a crucial role in various cancers. β1, 3-N-acetylglucosaminyltransferase 2, a polylactosamine synthase, is an important member of the glycosyltransferase family. Glycosyltransferases play a crucial role in various cancers. The biological function and regulatory mechanism of β3GNT2 in esophageal carcinoma (ESCA) is still poorly understood. Esophageal carcinoma (ESCA) is one of the most common cancers around the world [1]. ESCA, such as surgery, radiotherapy, and chemotherapy, the five-year survival rate of ESCA patients is still less than 20% [3]. This is mainly due to the lack of effective diagnostic and prognostic biomarkers. The mechanism involved in the occurrence and development of ESCA has not been fully elucidated. It is of great importance to explore the pathogenesis of ESCA and develop effective therapies for ESCA patients
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