MiR-491 attenuates cancer stem cells-like properties of hepatocellular carcinoma by inhibition of GIT-1/NF-κB-mediated EMT
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Hepatocellular carcinoma (HCC) is the most common liver malignancy. Current standard practices for treatment of HCC are less than satisfactory because of CSCs-mediated recurrence. For this reason, targeting CSCs, or cancer cells with CSCs-like properties, is a new approach for HCC treatment. As we reported previously, microRNA-491 (miR-491) is lower expressed in poorly differentiated HCC tissues relative to well-differentiated HCC tissues. Here, we further evaluate the effects of miR-491 on the CSCs-like properties by using HCC cell lines and HCC tissue samples. Our data showed that miR-491 had a negative relationship with CSCs-like properties both in cell lines and tissue samples of HCC. Further, miR-491 levels of non-recurrence HCC tissues were higher than those of recurrence HCC tissues. In HCC cell lines, nuclear factor kappa B (NF-κB)/snail pathway was involved in the epithelial to mesenchymal transition and the maintenance of CSCs-like properties. Overexpression of miR-491 targeted G-protein-coupled receptor kinase-interacting protein 1 (GIT-1), which blocked the activation of NF-κB by the inhibition of extracellular signal-regulated kinases (ERKs). Such process attenuated the CSCs-like properties in HCC cells. Our results point to a previously undefined mechanism by which miR-491 decreases CSCs-like properties and help to identify potential targets for the therapy of HCCs.
KeywordsHepatocellular carcinoma Cancer stem cells-like properties Epithelial to mesenchymal transition microRNA-491 G-protein-coupled receptor kinase-interacting protein 1 Nuclear factor kappa B
The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA) for editing. This work was supported by the Natural Science Foundations of China (81272713, 81100253, and 81273114).
Conflicts of interest
The authors declare they have no competing financial interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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