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.
Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family members are expressed in various cancers and may be associated with FTC progression. In this study, we measured ST8SIA family expression in two FTC cell lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1 cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated in the highly invasive FTC-238 cells and FTC tissues. Additionally, ST8SIA4 inhibited proliferation, migration and invasion of FTC both in vitro and in vivo. miR-146a and miR-146b were previously shown to be upregulated in thyroid carcinoma, and bioinformatics analyses indicated that miR-146a and miR-146b inhibit ST8SIA4. We found that miR-146a and miR-146b were significantly upregulated in FTC and promoted tumour progression. Furthermore, ST8SIA4 restoration decreased the invasiveness of miR-146a/b-overexpressing FTC-133 cells, and ST8SIA4 suppression reversed the effects of miR-146a/b inhibition in FTC-238 cells. We showed that miR-146a/b activated the PI3K-AKT-mTOR signalling pathway at least partially via suppression of ST8SIA4. Thus, our results demonstrate that miR-146a and miR-146b promote proliferation, migration and invasion of FTC via inhibition of ST8SIA4.
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