The expression and mechanism of α-1,3-fucosyltransferase IV in liver cancer metastasis

Abstract

Abstract: Objective To investigate the expression and mechanism of α-1,3-fucosyltransferase IV in liver cancer metastasis. Methods The expression of FUT4 in liver cancer cell lines exhibiting different metastatic potentials was detected by quantitative Real-time PCR (qRT-PCR). The epithelial-mesenchymal transition (EMT) model was established by stimulating human liver cancer cell line MHCC97L with transforming growth factor-β1 (TGF-β1). Morphologic change was observed by phase-contrast microscope. The expression of mRNAs and proteins of EMT markers were detected by qRT-PCR and Western blot, respectively. The expression of FUT4 was detected by qRT-PCR. The expression levels and co-expression genes of FUT4 in primary liver cancer samples with and without metastasis were investigated using Human Cancer Metastasis Database (HCMDB). Enrichment analysis of KEGG pathways was performed by OmicsBean. Results The mRNA expression levels of FUT4 were significantly upregulated in MHCC97H and HCCLM3, two liver cancer cell lines exhibited high metastatic potential, when compared with liver cancer cell line, MHCC97L, which exhibited low metastatic potential (P<0.01), fold changes were 4.99 and 6.08, respectively. After TGF-β1 treatment, MHCC97L cells were spindle-shaped and the mRNA expression of E-cadherin was significantly reduced (P<0.001), however, the mRNA expressions of N-cadherin and vimentin were significantly increased (P<0.001). The proteins' expression of EMT markers were in parallel as the mRNAs' expression. FUT4 was overexpressed in TGF-β1-induced EMT model in MHCC97L when compared with that of the control (P<0.01), the fold change was 1.42. Bioinformatics analysis results further confirmed that mRNA expression level of FUT4 was significantly upregulated in primary liver cancer samples with metastasis compared with those without metastasis (P<0.01), suggesting that FUT4 might participate in the liver cancer metastasis and programmed by the co-expressing genes belonging to KEGG pathways such as transcriptional mis-regulation in cancer, regulation of actin cytoskeleton, and ECM-receptor interaction. Conclusion These findings not only suggest that high-level expression of FUT4 is closely related to EMT and metastasis of liver cancer, but also provide an insight on using FUT4 as a potential biomarker and target for the diagnosis and treatment of liver cancer metastasis.

Key words: α-1,3-fucosyltransferase IV, liver cancer, metastasis, epithelial-mesenchymal transition, co-expression

NI Lei, GUO Jian, YU Xue, ZHANG Ning, HAN Yi-ying, YANG Yu-ai, YANG Jian-ren, LI Chun-rui, JIA Juan, LIU Tian-hua. The expression and mechanism of α-1,3-fucosyltransferase IV in liver cancer metastasis[J]. Chinese Hepatolgy, 2021, 26(10): 1123-1127.

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