GCNT4 is Associated with Prognosis and Suppress Cell Proliferation in Gastric Cancer

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Sep 14

PMID 32922038

Citations 5

Authors

Hui Sun

Jinjia Chang

Min Ye

Weiwei Weng

Meng Zhang

Shujuan Ni

Cong Tan

Dan Huang

Lei Wang

Xiang Du

Mi-Die Xu

Weiqi Sheng

Affiliations

Soon will be listed here.

Abstract

Background: GCNT4 is a member of the glucosaminyl (N-acetyl) transferases family that has been implicated in multiple human malignancies. However, the role of GCNT4 in gastric cancer (GC) is unknown. In this present study, we aimed to explore the role and clinicopathological correlation of GCNT4 in GC.

Materials And Methods: We first evaluated the dysregulation of GCNT4 in The Cancer Genome Atlas (TCGA) and then we performed RT-qPCR and immunohistochemistry to validate the results in a cohort of in-house patients. The clinicopathological correlation and function of GCNT4 in GC were also analysed.

Results: GCNT4 was found to be significantly downregulated in GC. In addition, GCNT4 expression correlated with tumour depth, nervous invasion and pathological tumor-node-metastasis (pTNM) stage. Moreover, lower GCNT4 levels conferred poor overall survival (OS) and disease-free survival (DFS) to GC patients. Multivariate Cox regression analysis revealed that GCNT4 protein expression is an independent prognostic factor for OS in patients with GC. Further functional experimental results revealed that overexpression of GCNT4 appears to halt GC cell proliferation and the cell cycle.

Conclusion: Altogether, these findings indicated that GCNT4 regulates the GC cell cycle and have important implications for the selection of therapeutic targets to prevent tumour proliferation.

Citing Articles

Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes.

Sun H, Wang X, Zhang X, Wang X, Tan C, Weng W BMC Cancer. 2022; 22(1):1188.

PMID: 36401232 PMC: 9675203. DOI: 10.1186/s12885-022-10312-0.

Identification of an amino acid metabolism-associated gene signature predicting the prognosis and immune therapy response of clear cell renal cell carcinoma.

Zhang F, Lin J, Zhu D, Tang Y, Lu Y, Liu Z Front Oncol. 2022; 12:970208.

PMID: 36158645 PMC: 9493051. DOI: 10.3389/fonc.2022.970208.

Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis.

Zhang C, Ji X, Chen Z, Yao Z J Immunol Res. 2022; 2022:1917585.

PMID: 35692504 PMC: 9184171. DOI: 10.1155/2022/1917585.

A Novel Glycosyltransferase-Related Gene Signature for Overall Survival Prediction in Patients with Ovarian Cancer.

Wang L Int J Gen Med. 2022; 14:10337-10350.

PMID: 34992448 PMC: 8717217. DOI: 10.2147/IJGM.S332945.

MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway.

Hu W, Zheng X, Liu J, Zhang M, Liang Y, Song M Bioengineered. 2021; 12(2):11634-11647.

PMID: 34696660 PMC: 8810009. DOI: 10.1080/21655979.2021.1995099.

References

Rinaldi M, Dreesen L, Hoorens P, Li R, Claerebout E, Goddeeris B . Infection with the gastrointestinal nematode Ostertagia ostertagi in cattle affects mucus biosynthesis in the abomasum. Vet Res. 2011; 42:61. PMC: 3102617. DOI: 10.1186/1297-9716-42-61. View

Liu T, Zhang S, Chen J, Jiang K, Zhang Q, Guo K . The transcriptional profiling of glycogenes associated with hepatocellular carcinoma metastasis. PLoS One. 2014; 9(9):e107941. PMC: 4169445. DOI: 10.1371/journal.pone.0107941. View

Chao C, Wu P, Huang H, Chung H, Chou Y, Cai B . Downregulation of miR-199a/b-5p is associated with GCNT2 induction upon epithelial-mesenchymal transition in colon cancer. FEBS Lett. 2017; 591(13):1902-1917. DOI: 10.1002/1873-3468.12685. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

Xu M, Dong L, Qi P, Weng W, Shen X, Ni S . Pituitary tumor-transforming gene-1 serves as an independent prognostic biomarker for gastric cancer. Gastric Cancer. 2015; 19(1):107-15. DOI: 10.1007/s10120-015-0459-2. View

Gonzalez-Vallinas M, Molina S, Vicente G, Zarza V, Martin-Hernandez R, Garcia-Risco M . Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer. PLoS One. 2014; 9(6):e98556. PMC: 4043684. DOI: 10.1371/journal.pone.0098556. View

Gonzalez-Vallinas M, Vargas T, Moreno-Rubio J, Molina S, Herranz J, Cejas P . Clinical relevance of the differential expression of the glycosyltransferase gene GCNT3 in colon cancer. Eur J Cancer. 2014; 51(1):1-8. DOI: 10.1016/j.ejca.2014.10.021. View

Zhang H, Meng F, Wu S, Kreike B, Sethi S, Chen W . Engagement of I-branching {beta}-1, 6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-{beta} signaling. Cancer Res. 2011; 71(14):4846-56. PMC: 3903410. DOI: 10.1158/0008-5472.CAN-11-0414. View

Rao C, Janakiram N, Madka V, Kumar G, Scott E, Pathuri G . Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer. Cancer Res. 2016; 76(7):1965-74. DOI: 10.1158/0008-5472.CAN-15-2820. View

10.

Kim M, Kim J, Jang H, Kim H, Lee C, Noh S . LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer. Cancer Res. 2008; 68(17):7147-55. DOI: 10.1158/0008-5472.CAN-08-0667. View

11.

Nakamura K, Yamashita K, Sawaki H, Waraya M, Katoh H, Nakayama N . Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC. Anticancer Res. 2015; 35(3):1411-21. View

12.

Xu M, Wang Y, Weng W, Wei P, Qi P, Zhang Q . A Positive Feedback Loop of lncRNA- and FOXM1 Facilitates Gastric Cancer Growth and Invasion. Clin Cancer Res. 2016; 23(8):2071-2080. DOI: 10.1158/1078-0432.CCR-16-0742. View

13.

Sun H, Ni S, Ye M, Weng W, Zhang Q, Zhang M . Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer. J Cancer. 2018; 9(24):4642-4649. PMC: 6299386. DOI: 10.7150/jca.27686. View

14.

Satomura Y, Sawabu N, Takemori Y, Ohta H, Watanabe H, Okai T . Expression of various sialylated carbohydrate antigens in malignant and nonmalignant pancreatic tissues. Pancreas. 1991; 6(4):448-58. DOI: 10.1097/00006676-199107000-00012. View

15.

Vajaria B, Patel P . Glycosylation: a hallmark of cancer?. Glycoconj J. 2016; 34(2):147-156. DOI: 10.1007/s10719-016-9755-2. View

16.

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

17.

Petrosyan A, Holzapfel M, Muirhead D, Cheng P . Restoration of compact Golgi morphology in advanced prostate cancer enhances susceptibility to galectin-1-induced apoptosis by modifying mucin O-glycan synthesis. Mol Cancer Res. 2014; 12(12):1704-16. PMC: 4272641. DOI: 10.1158/1541-7786.MCR-14-0291-T. View

18.

Wang Y, Xu M, Weng W, Wei P, Yang Y, Du X . BCL6 is a negative prognostic factor and exhibits pro-oncogenic activity in ovarian cancer. Am J Cancer Res. 2015; 5(1):255-66. PMC: 4300693. View

19.

Wu F, Yuan G, Chen J, Wang C . Network analysis based on TCGA reveals hub genes in colon cancer. Contemp Oncol (Pozn). 2017; 21(2):136-144. PMC: 5611503. DOI: 10.5114/wo.2017.68622. View

20.

Mikami J, Tobisawa Y, Yoneyama T, Hatakeyama S, Mori K, Hashimoto Y . I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling. Cancer Sci. 2015; 107(3):359-68. PMC: 4814258. DOI: 10.1111/cas.12859. View