Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second major subtype of primary liver cancer and has caused more and more attention with increasing incidence and mortality worldwide. Our previous study found that bisecting N-glycans are commonly increased in ICC, while the effects and potential functions of bisecting GlcNAc in ICC are still largely unclear. In this study, we further confirmed that the structures of bisecting GlcNAc were significantly up-regulated in ICC compared with paracancer tissues by glycoproteomic data and lectin histochemistry. The expression of its glycosyltransferase MGAT3 was also up-regulated in ICC tissues at both mRNA and protein levels, and expression of MGAT3 is negatively correlated with overall survival explored by bioinformatic analyses and published datasets from 255 patients. Next, the silencing of MGAT3 could inhibit the growth and invasion of ICC cells, and overexpressing of MGAT3 only promoted ICC cell invasion. Further glycoproteomic analysis showed that the commonly glycoproteins modified by bisecting GlcNAc after MGAT3-overexpression in two ICC cell lines were mainly involved in cell movement-related biological processes, such as cell adhesion, integrin-related and ECM-receptor interaction. This study sheds light on the potential effects of bisecting GlcNAc in ICC cells and suggests that MGAT3 might be used as a potential target in the therapy of ICC.
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Data Availability
The mass spectrometry data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD035321.
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Acknowledgements
This work was supported by the National Key Research and Development Program of China (No. 2019YFA0905200), National Natural Science Foundation of China (No. 81773180, 91853123, 32101192, 21705127 and 81800655), and China Postdoctoral Science Foundation (No. 2019TQ0260 and 2019M663798).
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W.D. and S.S. designed the experiments; L.H. collected the tissue samples; W.D. and C.L. performed experiments with help from P.L., J.L, J.L.; W.D., C.L., Z.C and J.L., J.S., analyzed data; W.D., J.L., P.L., L.D., M.X., Z.Y., and S.S. wrote the paper with help from all authors.
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All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. This study does not involve experiments of animal models.
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Tissue samples were prospectively collected from patients undergoing ICC resection at the First Affiliated Hospital of Xi’an Jiaotong University, China. The study was approved by Human Ethics Committee at the First Affiliated Hospital of Xi’an Jiaotong University, and written informed consents were obtained from all participants.
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Dan, W., Li, C., Li, J. et al. Glycoproteomic analysis reveals the effects of bisecting GlcNAc in intrahepatic cholangiocarcinoma. Glycoconj J 39, 737–745 (2022). https://doi.org/10.1007/s10719-022-10085-5
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DOI: https://doi.org/10.1007/s10719-022-10085-5