The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer

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.

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

“…Historically identified as a member of the glycosyltransferase family, GALNT2 was found to modulate adipogenesis and insulin signaling in adipocytes, impacting metabolic processes associated with obesity and diabetes ( 62 ). Its importance also extends to tumor development and progression, emphasizing its role in both metabolic and oncological pathways ( 63 ). Elevated GALNT2 levels are linked to unfavorable outcomes in patients with glioblastoma multiforme (GBM).…”

Hub Genes in Non-Small Cell Lung Cancer Regulatory Networks

“…Oncogenic STRAP [ 75 ] inhibits E-cadherin and P21 ( CIP1 ) through modulation of transcription factor SP1, contributing to tumor progression [ 76 ]. GALNT2 functions as an oncogenic driver in NSCLC proliferation, migration, and invasion in vitro, and its knockdown restrained tumor formation in vivo [ 77 ]. PFKP, involved in metabolism, is a suggested oncogene in lung cancer [ 78 ].…”

Three-dimensional genome landscape comprehensively reveals patterns of spatial gene regulation in papillary and anaplastic thyroid cancers: a study using representative cell lines for each cancer type

“…We performed preparation of library and sequencing using the BioGenius Genomics Platform following manufacturers’ instructions. We processed all cell lines using the same protocols for preparation of library and sequencing [ 37 – 39 ]. We prepared WGS libraries from 1 μg DNA using the Illumina TruSeq PCR-free DNA sample preparation kits with an average insert size of 350 bp.…”