Previous studies have shown that high levels of PLK1 are expressed in HCC, and PLK1 inhibitors are being tested in clinical trials. However, the mechanisms, which regulate PLK1 expression in HCC, have not been clarified. Here, we show that induction of let-7b over-expression inhibits the PLK1-regulated luciferase activity in HEK-293T cells, and decreases the levels of PLK1 expression in HCC cells. Furthermore, the levels of let-7b expression were negatively correlated with PLK1 expression in HCC tissues. Let-7b over-expression inhibited the proliferation of HCC cells and promoted their apoptosis, which were partially rescued by increased PLK1 expression. Let-7b over-expression decreased the levels of PLK1, CDC25C and Survivin phosphorylation and CDC2, β-catenin, TCF-4 expression, which were mitigated by increased PLK1 expression in MHCC-97H cells. Let-7b over-expression inhibited the development and growth of implanted HCC tumors in mice by decreasing PLK1 and Survivin expression in the tumors. Together, our data indicated that let-7b targeted PLK1 to inhibit HCC growth and induce their apoptosis by attenuating the PLK1-mediated Survivin phosphorylation. Our findings may provide new insights into the pathogenesis of HCC.
Keywords: Apoptosis; Let-7b; Polo-like kinase 1; Proliferation; Survivin.
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