| Summary: | <p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression.</p> <p>Methods and results</p> <p>We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion <it>in vitro</it>. Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion <it>in vitro</it>. Moreover, BMI-1 knockdown inhibited <it>in vitro </it>EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1).</p> <p>Conclusion</p> <p>These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.</p>
|
|---|
