B4GALNT4促进肺腺癌细胞增殖、迁移和侵袭能力

doi:10.6040/j.issn.1671-7554.0.2024.0768

摘要/Abstract

摘要： 目的评估4-N-乙酰半乳糖氨基转移酶4(β-1, 4-N-acetyl-galactosaminyltransferases Ⅳ, B4GALNT4)在肺腺癌中的作用。方法通过肿瘤基因图谱(The Cancer Genome Atlas, TCGA)数据库分析B4GALNT4在肺腺癌中的表达,探讨B4GALNT4与肺腺癌患者预后的关系。应用免疫组化和Western blotting研究B4GALNT4在肺腺癌组织中的表达,通过小干扰RNA瞬时转染在A549和H1299细胞中敲减B4GALNT4并进行功能实验,应用CCK-8、EdU实验检测肺腺癌细胞的增殖潜力。通过细胞划痕实验、Transwell迁移和侵袭实验,检测肺腺癌细胞的迁移和侵袭能力。应用Western blotting探讨B4GALNT4发挥功能的潜在分子机制。结果 TCGA数据库分析结果显示,与癌旁正常组织相比,B4GALNT4基因在肺腺癌组织中的表达升高(P<0.05),且B4GALNT4高表达与患者的不良预后相关(P<0.01);免疫组化及Western blotting结果显示,肺腺癌组织中B4GALNT4蛋白水平较其癌旁正常组织升高;在A549和H1299细胞系中敲减B4GALNT4会抑制肺腺癌细胞的增殖、迁移和侵袭能力(P<0.05),其机制可能与PI3K/AKT/mTOR通路密切相关。结论 B4GALNT4在肺腺癌的发展中可能起到促癌基因的作用,该作用可能通过影响PI3K/AKT/mTOR信号通路中关键蛋白的表达水平从而发挥作用。

关键词: 4-N-乙酰半乳糖氨基转移酶, 肺腺癌, 增殖, 迁移, 侵袭, PI3K/AKT/mTOR信号通路

Abstract: Objective To evaluate the role of β-1,4-N-acetyl-galactosaminyltransferases Ⅳ(B4GALNT4)in lung adenocarcinoma. Methods The Cancer Genome Atlas(TCGA)database was used to analysis the expression of B4GALNT4 in lung adenocarcinoma, and the relationship between prognosis and the expression level of this gene was explored. Immunohistochemistry and Western blotting were used to detect the expression of B4GALNT4 in lung adenocarcinoma tissues. The functional experiments involved the knockdown of B4GALNT4 in A549 and H1299 cells using transient transfection with small interfering RNA. Subsequently, the proliferative capacity of these lung adenocarcinoma cells was assessed through CCK-8 and EdU assays. Then, cell scratch assay, transwell migration, and invasion assay were utilized to detect the migration and invasion ability of lung adenocarcinoma cells. Western blotting was conducted to uncover the underlying molecular mechanisms in these processes. Results The TCGA database showed that compared with adjacent tissues, the B4GALNT4 gene had significantly higher levels in lung adenocarcinoma tissues (P<0.05), which was correlated with the poor prognosis of patients(P<0.01). Immunohistochemistry and Western blotting showed that B4GALNT4 protein levels were elevated in lung adenocarcinoma tissues compared to adjacent normal tissues. Furthermore, knockdown of B4GALNT4 in A549 and H1299 cell lines significantly inhibited the proliferation, migration, and invasion abilities of lung adenocarcinoma cells(P<0.05), and the mechanism might be closely related to the PI3K/AKT/mTOR pathway. Conclusion B4GALNT4 might play a role as a pro-oncogene in the development of lung adenocarcinoma, and this role might be mediated by affecting the expression levels of key proteins in the PI3K/AKT/mTOR signaling pathway.

Key words: β-1, 4-N-acetylgalactosaminyltransferases, Lung adenocarcinoma, Proliferation, Migration, Invasion, PI3K/AKT/mTOR signaling pathway

中图分类号:

R734

韩觉明,王晖,吴倩,郑慧玲,朱琳. B4GALNT4促进肺腺癌细胞增殖、迁移和侵袭能力[J]. 山东大学学报 (医学版), 2025, 63(7): 23-31.

HAN Jueming, WANG Hui, WU Qian, ZHENG Huiling, ZHU Lin. B4GALNT4 promotes proliferation, migration and invasion of lung adenocarcinoma cells[J]. Journal of Shandong University (Health Sciences), 2025, 63(7): 23-31.

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