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Comprehensive N-glycan profiles of hepatocellular carcinoma reveal association of fucosylation with tumor progression and regulation of FUT8 by microRNAs

Lei Cheng, Shuhang Gao, Xiaobo Song, Weijie Dong, Huimin Zhou, Lifen Zhao and Li Jia _

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Oncotarget. 2016; 7:61199-61214. https://doi.org/10.18632/oncotarget.11284

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Abstract

Lei Cheng1,2,*, Shuhang Gao3,*, Xiaobo Song4, Weijie Dong5, Huimin Zhou6, Lifen Zhao1, Li Jia1

1College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China

2Department of Laparoscopic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China

3Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China

4Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

5Department of Biochemistry, Dalian Medical University, Dalian 116044, Liaoning Province, China

6Department of Microbiology, Dalian Medical University, Dalian 116044, Liaoning Province, China

*These authors contributed equally to this work

Correspondence to:

Li Jia, email: [email protected]

Keywords: fucosyltransferase (FUT) gene, human hepatocellular carcinoma cell lines, tumor progression, microRNAs

Received: February 05, 2016     Accepted: August 09, 2016     Published: August 13, 2016

ABSTRACT

Glycosylation has significant effects on cancer progression. Fucosylation is one of the most important glycosylation events involved in hepatocellular carcinoma (HCC). Here, we compared N-glycan profiles of liver tumor tissues and adjacent tissues of 27 HCC patients to reveal the association between fucosylation and HCC progression, as well as verified the potential role of miRNA in regulating fucosylation. Mass spectrometry (MS) analysis showed pronounced differences of the N-glycosylation patterns and fucosylated N-glycans between the adjacent and tumor tissues. Different fucosyltransferase (FUT) genes were also identified in adjacent and tumor tissues, and two HCC cell lines with different metastatic potential. High-level expression of FUT8 was detected in tumor tissues and highly metastatic HCC cells. Altered levels of FUT8 in HCC cell lines significantly linked to the malignant behaviors of proliferation and invasion in vitro. Furthermore, using microRNA array, we identified FUT8 as one of the miR-26a, miR-34a and miR-146a-targeted genes. An inverse correlation was revealed between the expression levels of FUT8 and these miRNAs. Luciferase reporter assay demonstrated these miRNAs specifically interacted with the 3′UTR of FUT8 and subsequently down-regulated FUT8 expression-level. The forced expression of these miRNAs was able to induce a decrease in FUT8 levels and thereby to suppress HCC cells progression. Altogether, our results indicate that fucosylated N-glycan and FUT8 levels can be used as markers for evaluating HCC progression, as well as miRNAs may be involved in inhibition of fucosylation machinery through targeting FUT8.


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