Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, 30 South Renmin Road, Shiyan, 442000, Hubei, China.
Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.
Cell Mol Biol Lett. 2022 Sep 4;27(1):71. doi: 10.1186/s11658-022-00378-w.
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.
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.
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.
These findings suggest that GALNT2 is an oncogene in NSCLC and has the potential as a target for NSCLC therapy.
启动粘蛋白型 O-糖基化的 N-乙酰半乳糖胺转移酶（GALNTs）与肿瘤的发生和发展密切相关。然而，目前缺乏对非小细胞肺癌（NSCLC）中 GALNTs 的全面分析。
利用公共数据库分析 GALNT 家族成员在 NSCLC 中的表达谱和预后价值。通过增益和缺失功能实验来评估 GALNT2 在 NSCLC 中的生物学功能。采用高通量测序和生物信息学方法来揭示 GALNT2 的调控机制。
在 GALNTs 的家族成员中，只有 GALNT2 在 NSCLC 组织中频繁过表达，并且与不良预后呈正相关。体外实验表明，GALNT2 敲低抑制 NSCLC 细胞的增殖、迁移和侵袭，但诱导细胞凋亡和细胞周期停滞。相应地，GALNT2 的过表达则产生相反的效果。体内实验表明，GALNT2 敲低抑制裸鼠肿瘤的形成。机制研究表明，GALNT2 修饰了 ITGA5 的 O-糖基化，影响了 PI3K/Akt 和 MAPK/ERK 通路的激活。进一步的研究表明，miR-30d 是 GALNT2 的负调控因子。
这些发现表明，GALNT2 是 NSCLC 中的一种癌基因，具有作为 NSCLC 治疗靶点的潜力。
