miR-200b inhibits proliferation and metastasis of breast cancer by targeting fucosyltransferase IV and α1,3-fucosylated glycans

Abstract

Aberrant protein fucosylation is associated with cancer malignancy. Fucosyltransferase IV (FUT4) is the key enzyme catalyzing the biosynthesis of α1,3-linkage fucosylated glycans carried by glycoproteins on the cell surface, such as the tumor-associated sugar antigen Lewis Y (LeY). An abnormal increase in the levels of FUT4 and LeY is observed in many cancers and correlated with cell proliferation and metastasis. Some microRNAs (miRNAs) are known to negatively regulate gene expression. FUT4 is an oncogenic glycogene, and thus it is important to identify the specific miRNA targeting FUT4. In current study, we first identified miR-200b as a specific miRNA that inhibited FUT4 expression. We found that miR-200b level was decreased, whereas that of FUT4 was increased in tissues and serum of breast cancer compared with that in the control by real-time PCR, western blotting and enzyme-linked immunosorbent assay. The alterations of miR-200b and FUT4 level were recovered after chemotherapy. The results also showed that miR-200b suppressed FUT4 expression and inhibited tumor growth and metastasis in MCF-7 and MDA-MB-231 breast cancer cells, as well as in the xenografted tumor tissues and metastatic lung tissues. miR-200b decreased the α1,3-fucosylation and LeY biosynthesis on epidermal growth factor receptor (EGFR), as well as inactivation of EGFR and downstream phosphoinositide-3 kinase/Akt signaling pathway. In conclusion, the study highlights that FUT4 could apply as a novel target for miR-200b that suppress the proliferation and metastasis of breast cancer cells by reducing α1,3-fucosylation and LeY biosynthesis of glycoproteins. miR-200b and FUT4 are potential diagnostic and therapeutic targets for breast cancer.

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

“…Numerous studies have revealed that an miRNA subset is aberrantly expressed in nearly all human cancer types, including breast cancer (32)(33)(34). The dysregulation of miRNAs is involved in the tumorigenesis and progression of breast cancer due to their negative regulation of downstream target genes (35)(36)(37). It is generally accepted that miRNAs may have tumor-suppressive or oncogenic roles in breast cancer and participate in the regulation of numerous cellular biological processes (16,38,39).…”

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway

“…Aberrant fucosylation and dysregulation of FUTs have been frequently found in human cancer [29,30]. FUT4 could catalyze α1, 3-fucosylation that is particularly involved in a variety of pathological processes and in cancer biology [31]. Importantly, cancer-related CD15/ FUT4 is overexpressed in most of metastatic colorectal cancer (mCRC) patients and participates in cetuximab or bevacizumab mechanisms of resistance in mCRC patients [32].…”

miR-1290 stimulates proliferation of gastric cancer by targeting SP1 with overexpression of fucosyltransferase IV and α1, 3-fucosylated glycans

“…Recently, our lab was found a critical role of mir200b in the inhibition of breast cancer proliferation and metastasis by targeting fucosyltransferase IV and α 1,3-fucosylated glycans [37]. Previously, we reported that Rg3 drug stimulated gastric cancer cell apoptosis through FUT4 fucosylation by regulating SP1 and HSF1 expressions, which suggested oncogenic role of CagA in development of H. pylori associated gastric cancer [34], [35].…”