Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (7): 23-31.doi: 10.6040/j.issn.1671-7554.0.2024.0768

Previous Articles     Next Articles

B4GALNT4 promotes proliferation, migration and invasion of lung adenocarcinoma cells

HAN Jueming, WANG Hui, WU Qian, ZHENG Huiling, ZHU Lin   

  1. Department of Pulmonary and Critial Care Medicine, The Second Hospital of Shandong University, Jinan 250031, Shandong, China
  • Published:2025-07-08

PDF (PC)

76

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

CLC Number: 

  • R734
[1] Wang Y, Yan Q, Fan C, et al. Overview and countermeasures of cancer burden in China[J]. Sci China Life Sci, 2023, 66(11): 2515-2526.
[2] Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment[J]. Mayo Clin Proc, 2019, 94(8): 1623-1640.
[3] Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024[J]. CA A Cancer J Clinicians, 2024, 74(1): 12-49.
[4] Varki A. Biological roles of glycans[J]. Glycobiology, 2017, 27(1): 3-49.
[5] Baba H, Kanda M, Sato Y, et al. Expression and malignant potential of B4GALNT4 in esophageal squamous cell carcinoma[J]. Ann Surg Oncol, 2020, 27(9): 3247-3256.
[6] Fan AY, Zhang YY, Cheng JT, et al. A novel prognostic model for prostate cancer based on androgen biosynthetic and catabolic pathways[J]. Front Oncol, 2022, 12: 950094. doi:10.3389/fonc.2022.950094
[7] Hsu WM, Che MI, Liao YF, et al. B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration and invasion via βı integrin signaling in neuroblastoma[J]. Am J Pathol, 2011, 179(3): 1394-1404.
[8] Glaviano A, Foo ASC, Lam HY, et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer[J]. Mol Cancer, 2023, 22(1): 138. doi:10.1186/s12943-023-01827-6
[9] Yu FY, Zhao XY, Li MT, et al. SLITRK6 promotes the progression of lung adenocarcinoma by regulating PI3K/AKT/mTOR signaling and Warburg effect[J]. Apoptosis, 2023, 28(7/8): 1216-1225.
[10] Li KY, Quan LL, Huang F, et al. ADAM12 promotes the resistance of lung adenocarcinoma cells to EGFR-TKI and regulates the immune microenvironment by activating PI3K/Akt/mTOR and RAS signaling pathways[J]. Int Immunopharmacol, 2023, 122: 110580. doi:10.1016/j.intimp.2023.110580
[11] Huang SC, Zhao HC, Lou XL, et al. TM6SF1 suppresses the progression of lung adenocarcinoma and M2 macrophage polarization by inactivating the PI3K/AKT/mtor pathway[J]. Biochem Biophys Res Commun, 2024, 718: 149983. doi:10.1016/j.bbrc.2024.149983
[12] Moremen KW, Tiemeyer M, Nairn AV. Vertebrate protein glycosylation: diversity, synthesis and function[J]. Nat Rev Mol Cell Biol, 2012, 13(7): 448-462.
[13] Huang J, Liang JT, Huang HC, et al. Beta1, 4-N-acetylgalactosaminyltransferase III enhances malignant phenotypes of colon cancer cells[J]. Mol Cancer Res, 2007, 5(6): 543-552.
[14] Tan ZQ, Jiang YZ, Liang L, et al. Dysregulation and prometastatic function of glycosyltransferase C1GALT1 modulated by cHP1BP3/miR-1-3p axis in bladder cancer[J]. J Exp Clin Cancer Res, 2022, 41(1): 228. doi:10.1186/s13046-022-02438-7
[15] Liu SQ, Su YJ, Qin MB, et al. Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules[J]. Int J Oncol, 2013, 42(2): 617-626.
[16] 邹瑜琳. 小分子核酸AS-tRF通过靶向B4GALNT4调节内皮细胞炎症的作用和机制 [D]. 青岛: 青岛大学, 2022.
[17] Fukushima K, Satoh T, Baba S, et al. Alpha 1, 2-fucosylated and beta-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer[J]. Glycobiology, 2010, 20(4): 452-460.
[18] Adamczyk B, Jin CS, Polom K, et al. Sample handling of gastric tissue and O-glycan alterations in paired gastric cancer and non-tumorigenic tissues[J]. Sci Rep, 2018, 8: 242. doi:10.1038/s41598-017-18299-6
[19] Kitamura N, Guo SC, Sato T, et al. Prognostic significance of reduced expression of beta-N-acetylgalactosaminylated N-linked oligosaccharides in human breast cancer[J]. Int J Cancer, 2003, 105(4): 533-541.
[20] Martini M, De Santis MC, Braccini L, et al. PI3K/AKT signaling pathway and cancer: an updated review[J]. Ann Med, 2014, 46(6): 372-383.
[21] Lawrence MS, Stojanov P, Mermel CH, et al. Discovery and saturation analysis of cancer genes across 21 tumour types[J]. Nature, 2014, 505(7484): 495-501.
[22] Turdo A, DAccardo C, Glaviano A, et al. Targeting phosphatases and kinases: how to checkmate cancer[J]. Front Cell Dev Biol, 2021, 9: 690306. doi:10.3389/fcell.2021.690306
[23] Yuan YQ, Long HZ, Zhou ZW, et al. PI3K-AKT-targeting breast cancer treatments: natural products and synthetic compounds[J]. Biomolecules, 2023, 13(1): 93. doi:10.3390/biom13010093
[24] Zhu KR, Wu YQ, He P, et al. PI3K/AKT/mTOR-targeted therapy for breast cancer[J]. Cells, 2022, 11(16): 2508. doi:10.3390/cells11162508
[25] Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer[J]. Nat Rev Cancer, 2002, 2(7): 489-501.
[26] Yu L, Wei J, Liu PD. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer[J]. Semin Cancer Biol, 2022, 85: 69-94. doi:10.1016/j.semcancer.2021.06.019
[27] Zhou BP, Hu MC, Miller SA, et al. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway[J]. J Biol Chem, 2000, 275(11): 8027-8031.
[28] Dillon RL, White DE, Muller WJ. The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer[J]. Oncogene, 2007, 26(9): 1338-1345.
[29] Zhang YQ, Ng PK, Kucherlapati M, et al. A pan-cancer proteogenomic atlas of PI3K/AKT/mTOR pathway alterations[J]. Cancer Cell, 2017, 31(6): 820-832.
[30] Ko JH, Um JY, Lee SG, et al. Conditioned media from adipocytes promote proliferation, migration, and invasion in melanoma and colorectal cancer cells[J]. J Cell Physiol, 2019, 234(10): 18249-18261.
[1] WANG Wei, WANG Yi-Feng, ZHANG Ling-Mei, LIN Qiong-Yan, HUANG Ju. umorigenicity and invasion of side population in human ovarian epithelial cancer OVCAR3 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 8-11.
[2] WANG Xiao-Lei, ZHANG Hai-Thao, ZHANG Hui, GUO Cheng-Hao. Protective effects of shuxuening injecta on vascular  endothelial  cell injury in vitro due to iodine excesses [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 38-.
[3] CAI Jiaying, WANG Jingting, WANG Zengping, WANG Jing, JIA Yanfei, MA Xiaoli. Effect of α5-nAChR on the expression of c-Fos in nucleus ambiguus in chronic stress-induced lung adenocarcinoma mice [J]. Journal of Shandong University (Health Sciences), 2025, 63(4): 69-74.
[4] ZHANG Jie, ZHANG Fangfang, WANG Jingnan, LI Zeyu, SONG Ying, LI Na. Expression of circ_0000144 in breast cancer and its effect on the proliferation, migration and invasion ability of breast cancer cells [J]. Journal of Shandong University (Health Sciences), 2025, 63(1): 35-42.
[5] WANG Jingting, WANG Jing, LU Yi, LI Jingtan, LI Qiang, JIA Yanfei, MA Xiaoli. Expression and correlation of α5-nAChR and MHC-I in lung adenocarcinoma [J]. Journal of Shandong University (Health Sciences), 2024, 62(5): 72-78.
[6] YANG Chuang, ZHANG Rongyu, SONG Bin, WANG Chengjun, ZHAO Wen, XUAN Tiantian, LI Jisheng. A rare case of lung adenocarcinoma complicated with bullous pemphigoid successfully treated with EGFR-TKI almonertinib [J]. Journal of Shandong University (Health Sciences), 2024, 62(12): 32-37.
[7] CAO Hualin, JIA Yanzhao, QU Li, YIN Xin. Impacts of CircFAT1 on the proliferation, apoptosis and radiosensitivity of nasopharyngeal carcinoma cells by regulating miR-296-3p/MAPRE1 axis [J]. Journal of Shandong University (Health Sciences), 2023, 61(9): 38-46.
[8] MENG Jianli, WANG Qinggang. Expression and potential mechanism of VPS72 in lung adenocarcinoma/ squamous cell carcinoma by integrated bioinformatics analysis [J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 40-49.
[9] JIN Shan, GAO Jie, XIE Yujiao, ZHAN Yao, DU Tiantian, WANG Chuanxin. Effects of methyltransferase PRMT5 on stabilizing USP15 to promote the occurrence and development of breast cancer [J]. Journal of Shandong University (Health Sciences), 2023, 61(7): 1-11.
[10] HE Jing, YAN Rugen, WU Zhihong, LI Changzhong. Effects of Xiaozheng Yiai decoction on the proliferation and migration of ovarian cancer SKOV3 cells [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 1-10.
[11] LIU Shibiao, ZHANG Shujun, LI Peilong, DU Lutao, WANG Chuanxin. The cg20657709 site methylation in the early detection of lung adenocarcinoma [J]. Journal of Shandong University (Health Sciences), 2023, 61(4): 18-25.
[12] DONG Xiangjun, LI Juan, KONG Xue, LI Peilong, ZHAO Wenjing, LIANG Yiran, WANG Lili, DU Lutao, WANG Chuanxin. Effects of circular RNA hsa_circ_0008591 on tumor biological behavior of breast cancer cells [J]. Journal of Shandong University (Health Sciences), 2023, 61(2): 78-87.
[13] ZHAO Qidi, WANG Kai, ZHAO Xiaogang, YAN Tao, WANG Yadong, DU Jiajun. Constructing and validating a prognostic model for patients with stage IIIB non-small cell lung cancer based on SEER database [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 23-37.
[14] ZHAO Ge, ZOU Cunhua, SONG Dongdong, ZHAO Shuping. Effects of tanshinone IIA on the proliferation and apoptosis of endometrial carcinoma cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 53-58.
[15] ZHANG Zhenwei, LI Jia, CHEN Keming. IGF2BP2/m6A/ITGA5 signal axis regulates the proliferation and migration of renal clear cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 74-84.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd