Sialyltransferase ST3GAL6 mediates the effect of microRNA-26a on cell growth, migration, and invasion in hepatocellular carcinoma through the protein kinase B/mammalian target of rapamycin pathway

唾液酸转移酶 ST3GAL6 通过蛋白激酶 B/哺乳动物雷帕霉素靶蛋白通路介导 microRNA-26a 对肝细胞癌细胞生长、迁移和侵袭的影响

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作者:Mingming Sun, Xuzi Zhao, Leilei Liang, Xufeng Pan, Hao Lv, Yongfu Zhao

Abstract

Aberrant sialylation profiles on the cell surface have been recognized for their potential diagnostic value in identifying the regulation of tumor properties in several cancers, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that the deregulation of microRNA (miRNA) is a common feature in human cancers. In this study, we found obvious upregulation of sialyltransferase ST3GAL6 both in HCC cell lines and in tissue samples. The altered expression of ST3GAL6 was found to correlate with cell proliferation, migration, and invasion ability in HCC. Further investigation showed that miR-26a negatively regulated ST3GAL6, inducing the suppression of cell proliferation, migration, and invasion in vitro. Moreover, we identified the protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway as the target of ST3GAL6 based on Western blot analysis. Analysis of a xenograft mouse model showed that miR-26a significantly reduced tumor growth by suppressing activation of the Akt/mTOR pathway by directly targeting ST3GAL6. In conclusion, these data indicate that ST3GAL6 promotes cell growth, migration, and invasion and mediates the effect of miR-26a through the Akt/mTOR signaling pathway in HCC.

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