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α-1,3-Fucosyltransferase-VII siRNA inhibits the expression of SLex and hepatocarcinoma cell proliferation.

Abstract：

:The increased expression of sialyl-Lewisx (SLex) epitope on the surface of tumor cells has been known for decades. However, genetic manipulation of the expression of SLex and the role of SLex in cancer cell proliferation remains to be fully elucidated. The present study suggested that the monoclonal antibody of SLex (KM93) significantly inhibited the proliferation of human hepatocarcinoma (HCC) cells. The expression levels of three sialyl‑Lewis oligosaccharide antigens, SLex, SLea and dimeric SLex (SDLex), were determined on the cell surface of the MHCC97 human HCC cell line. The expression of SLex was markedly higher in MHCC97 cells than in normal liver cells. The expression of SDLex was also relatively high, however, no significant difference was observed between normal liver cells and HCC cells. The expression of SLea was only detected in trace quantities. Fucosyltransferase (FUT) is the key enzyme of the fucosylation step in the biosynthesis of sialyl‑Lewis oligosaccharide antigens. Therefore, the present study investigated the expression of FUTs. It was found that the mRNA and protein expression levels of FUT7 were high in the MHCC97 HCC cell line compared with levels in normal liver cells. FUT6 was also expressed at a high level, although the difference was not statistically significant between MHCC97 cells and normal liver cells. No expression of FUT3 was detected. The results were consistent with the change insialyl‑Lewis antigens. The effects of FUT7 small interfering (si)RNA transfection on the expression of FUT7, expression of SLex and MHCC97 cell proliferation were also examined. Following FUT7 siRNA transfection, the expression of FUT7 was markedly downregulated, as determined by western blot and reverse transcription‑quantitative polymerase chain reaction methods. The results from flow cytometry showed that the synthesis of SLex was also inhibited, which was consistent with the downregulated expression of FUT7. MHCC97 cell proliferation was also significantly inhibited following FUT7 siRNA transfection, which was correlated with suppression of the S‑phase in cell cycle progression. By using inhibitors of various signaling pathways, it was found that the knockdown of FUT7 inhibited the activation of phospholipase Cγ (PLCγ) by inhibiting the translocation and phosphorylation of PLCγ. In conclusion, the results suggested that FUT7 has animportant functional role in human HCC cell proliferation by controlling cell cycle progression via the PLCγ/extracellular signal‑regulated kinase signaling pathway. The inhibition of SLex and FUT7 siRNA transfection may provide a novel therapeutic methodology to treat tumors that express SLex glycoconjugates.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Li D,Sun H,Bai G,Wang W,Liu M,Bao Z,Li J,Liu H

doi

10.3892/ijmm.2018.3850

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

2700-2708

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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α-1,3-Fucosyltransferase-VII siRNA inhibits the expression of SLex and hepatocarcinoma cell proliferation.