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miR-9 inhibits the metastatic ability of hepatocellular carcinoma via targeting beta galactoside alpha-2,6-sialyltransferase 1

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Abstract

Glycosylation of cell surface proteins regulates critical cellular functions, including invasion and metastasis in cancer cells. Emerging evidence has shown that microRNAs (miRNAs) are involved in regulating both the glycosylation modifications on cell surface and the progression of cancer. In this study, we investigated the role of miR-9 in α-2,6-linked sialylation and the metastasis of mouse hepatocellular carcinoma (HCC). According to array-based miRNA expression profiling data of HCC cell lines Hepa1–6, Hca-P, and Hca-F with different lymphatic metastatic capacities, reverse correlation was found between miR-9 expression levels and the metastatic potential in these HCC cells. Additionally, β-galactoside α-2,6-sialyltransferase 1 (St6gal1) expression level is associated negatively with miR-9 and positively with metastatic potential. Bioinformatics analysis indicated that miR-9 could target St6gal1, which was verified by luciferase reporter assays. miR-9 overexpression reduced expression of St6gal1, which subsequently suppressed HCC cells metastatic potential. Moreover, upregulation of miR-9 could inhibit integrin-β1/FAK-mediated cell motility and migration signaling in mouse HCC cells. Together, our results suggest that miR-9 could act as a tumor suppressor and regulate mouse HCC cells migration and invasion by inhibiting the α-2,6-linked sialylation. This finding may provide insight into the relationship between abnormal miRNA expression and aberrant cell surface glycosylation during tumor lymphatic metastasis.

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Funding

The authors would like to gratefully acknowledge support from the Natural Science Foundation of China (21502015, 31570802) and the Fundamental Research Funds for the Central Universities (DUT17JC21, DUT18ZD208, DUT18LAB09).

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Authors and Affiliations

  1. School of Life Science and Medicine, Dalian University of Technology, Panjin, 122406, China

    Yi Han, Yubo Liu, Xirao Fu, Qi Zhang, Huang Huang, Cheng Zhang, Wenli Li & Jianing Zhang

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  1. Yi Han
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  2. Yubo Liu
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  3. Xirao Fu
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  4. Qi Zhang
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  5. Huang Huang
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  7. Wenli Li
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  8. Jianing Zhang
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Correspondence to Jianing Zhang.

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Han, Y., Liu, Y., Fu, X. et al. miR-9 inhibits the metastatic ability of hepatocellular carcinoma via targeting beta galactoside alpha-2,6-sialyltransferase 1. J Physiol Biochem 74, 491–501 (2018). https://doi.org/10.1007/s13105-018-0642-0

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