Reference - Detail
|Author||Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, Sakuragi N.|
|Title||MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1.|
BACKGROUND: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.
METHODS AND RESULTS: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 in vitro. 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 in vitro. Moreover, BMI-1 knockdown inhibited in vitro 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).
CONCLUSION: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.
|MeSH||Cell Line, Tumor Cell Proliferation / drug effects Down-Regulation / genetics Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology* Epithelial-Mesenchymal Transition / genetics* Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans MicroRNAs / genetics MicroRNAs / physiology* Neoplasm Invasiveness Nuclear Proteins / antagonists & inhibitors Nuclear Proteins / genetics* Nuclear Proteins / metabolism Nuclear Proteins / physiology Phenotype Polycomb Repressive Complex 1 Proto-Oncogene Proteins / antagonists & inhibitors Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins / physiology RNA Interference RNA, Small Interfering / pharmacology Repressor Proteins / antagonists & inhibitors Repressor Proteins / genetics* Repressor Proteins / metabolism Repressor Proteins / physiology Sarcoma, Endometrial Stromal / genetics Sarcoma, Endometrial Stromal / metabolism Sarcoma, Endometrial Stromal / pathology*|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY ONCOLOGY|
|Human and Animal Cells||HHUA (RCB0658) HOUA-I (RCB0659)|