Globo H, a
cancer-associated
carbohydrate antigen, is highly expressed in various types of
cancers. However, the role of
Globo H in
hepatocellular carcinoma (HCC) remains elusive. In our study, we performed
glycan microarray analysis of 134 human serum samples to explore anti-
Globo H antibody changes and found that
Globo H is upregulated in hepatitis B virus (HBV)-positive HCC. Similarly, immunohistochemistry showed that
Globo H expression was higher in
tumors compared to normal tissues. In addition,
fucosyltransferase 2 (FUT2), the main synthetic
enzyme of
Globo H, was also increased in HCC cells overexpressing
HBV X protein (HBX). HBX plays an important role in promoting cell proliferation and may be related to increased levels of FUT2 and
Globo H. Furthermore, using
microRNA profiling, we observed that microRNA-15b (miR-15b) was downregulated in patients with HCC and confirmed association of FUT2 expression with expression of its product,
Globo H. Therefore, our results suggest that HBX suppressed the expression of miR-15b, which directly targeted FUT2 and then increased levels of
Globo H to enhance HCC cell proliferation. Additionally, proliferation of HBX-overexpressing HCC cells was significantly inhibited by treatment with
Globo H antibody in vitro. In xenograft animal experiments, we found that overexpression of miR-15b effectively suppressed
tumor growth. The newly identified HBX/miR-15b/FUT2/
Globo H axis suggests one possible molecular mechanism of HCC cell proliferation and represents a new potential therapeutic target for HCC treatment.