Construction and investigation of ß3GNT2-associated regulatory network in esophageal carcinoma.

BACKGROUND: Glycosyltransferases play a crucial role in various cancers. ß1, 3-N-acetylglucosaminyltransferase 2, a polylactosamine synthase, is an important member of the glycosyltransferase family. However, the biological function and regulatory mechanism of ß3GNT2 in esophageal carcinoma (ESCA) is still poorly understood. METHODS: The 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 ß3GNT2 in ESCA cell lines and tissues. In vitro assays and xenograft tumor models were utilized to evaluate the impact of ß3GNT2 on ESCA progression. The downstream effectors and upstream regulators of ß3GNT2 were predicted by online software and verified by functional experiments. RESULTS: We found that ß3GNT2 was highly expressed in ESCA tissues and positively correlated with poor prognosis in ESCA patients. ß3GNT2 expression was closely associated with the tumor size, TNM stage, and overall survival of ESCA patients. Functionally, ß3GNT2 promoted ESCA cell growth, migration, and invasion in vitro, as well as tumorigenesis in vivo. Mechanistically, ß3GNT2 knockdown decreased the expression of the polylactosamine on EGFR. Knockdown of ß3GNT2 also inhibited the JAK/STAT signaling pathway. Meanwhile, the JAK/STAT inhibitor could partly reverse the biological effects caused by ß3GNT2 overexpression. Moreover, ß3GNT2 expression was positively regulated by CREB1 and negatively regulated by miR-133b. Both CREB1 and miR-133b was involved in the ß3GNT2-mediated ESCA progression. CONCLUSIONS: Our study, for the first time, reveals the importance of ß3GNT2 in ESCA progression and offers a potential therapeutic target for ESCA.

C1GALT1, Negatively Regulated by miR-181d-5p, Promotes Tumor Progression via Upregulating RAC1 in Lung Adenocarcinoma.

Glycosyltransferases are frequently dysregulated in lung cancer. Core 1 ß 1, 3-galactosyltransferase 1 (C1GALT1), an enzyme highly expressed in various cancers, is correlated with tumor initiation and development. However, the role of C1GALT1 in lung cancer remains poorly understood. In this study, through bioinformatic analysis and clinical validation, we first discovered that C1GALT1 expression was upregulated in lung adenocarcinoma (LUAD) tissues and was closely related to poor prognosis in patients with LUAD. Gain- and loss-of-function experiments showed that C1GALT1 promoted LUAD cell proliferation, migration, and invasion in vitro, as well as tumor formation in vivo. Further investigation demonstrated that RAC1 expression was positively regulated by C1GALT1 in LUAD, whereas silencing Rac1 could reverse C1GALT1-induced tumor growth and metastasis. Moreover, miR-181d-5p was identified as a negative regulator for C1GALT1 in LUAD. As expected, the inhibitory effects of miR-181d-5p on LUAD cell proliferation, migration, and invasion were counteracted by restoration of C1GALT1. In summary, our results highlight the importance of the miR-181d-5p/C1GALT1/RAC1 regulatory axis during LUAD progression. Thus, C1GALT1 may serve as a potential therapeutic target for LUAD.