Article ; Online: The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer.
Cellular & molecular biology letters
2022 Volume 27, Issue 1, Page(s) 71
Abstract: Background: N-Acetylgalactosaminyltransferases (GALNTs), the enzymes that initiate mucin-type O-glycosylation, are closely associated with tumor occurrence and progression. However, a comprehensive analysis of GALNTs in non-small cell lung cancer (NSCLC) ...
| Abstract | Background: N-Acetylgalactosaminyltransferases (GALNTs), the enzymes that initiate mucin-type O-glycosylation, are closely associated with tumor occurrence and progression. However, a comprehensive analysis of GALNTs in non-small cell lung cancer (NSCLC) is lacking. Methods: The expression profiles and prognostic values of the GALNT family members in NSCLC were analyzed using publicly available databases. Gain- and loss-of-function experiments were applied to assess the biological function of GALNT2 in NSCLC. High-throughput sequencing and bioinformatics approaches were employed to uncover the regulatory mechanism of GALNT2. Results: Among the family members of GALNTs, only GALNT2 was frequently overexpressed in NSCLC tissues and was positively correlated with poor prognosis. In vitro assays showed that GALNT2 knockdown repressed NSCLC cell proliferation, migration, and invasion, but induced apoptosis and cell cycle arrest. Correspondently, GALNT2 overexpression exerted the opposite effects. In vivo experiments demonstrated that knockdown of GALNT2 restrained tumor formation in nude mice. Mechanistic investigations revealed that GALNT2 modified the O-glycosylation of ITGA5 and affected the activation of the PI3K/Akt and MAPK/ERK pathways. Further studies showed that miR-30d was a negative regulator of GALNT2. Conclusions: These findings suggest that GALNT2 is an oncogene in NSCLC and has the potential as a target for NSCLC therapy. |
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| MeSH term(s) | Animals ; Carcinogenesis/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Mice ; Mice, Nude ; N-Acetylgalactosaminyltransferases/metabolism ; Oncogenes ; Phosphatidylinositol 3-Kinases/metabolism ; Polypeptide N-acetylgalactosaminyltransferase |
| Chemical Substances | N-Acetylgalactosaminyltransferases (EC 2.4.1.-) |
| Language | English |
| Publishing date | 2022-09-04 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2108724-6 |
| ISSN | 1689-1392 ; 1689-1392 |
| ISSN (online) | 1689-1392 |
| ISSN | 1689-1392 |
| DOI | 10.1186/s11658-022-00378-w |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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