1887

Abstract

Pancreatic cancer is one of the leading causes of cancer-related mortality worldwide and is highly therapy-resistant, e.g. toward the standard chemotherapy gemcitabine. Glucocorticoids like dexamethasone (DEX) are often co-medicated to reduce inflammation and side effects of tumor growth and therapy. Our group showed DEX to be a potent stimulator of epithelial to mesenchymal transition (EMT), cancer progression and metastasis, but the underlying mechanisms are poorly understood. MicroRNAs are a group of small non-coding RNAs that post transcriptionally regulate gene expression. In this study, I evaluated the effect of DEX on the microRNA profile of pancreatic cancer cell lines. By microRNA array I observed a deregulation of several miRNAs. The most significantly deregulated miRNA, miR-XYZ was predicted to target key members of the TGFß pathway. Forced expression of this miR-XYZ by liposomal transfection of mimicsresulted in significant repression of TGFß-2 mRNA and protein levels. 3’UTR luciferasereporter- and site-directed mutagenesis assays confirmed TGFß-2 to be a direct target of miR-XYZ. Functionally, I found that miR-XYZ significantly reduced proliferation, migration and colony formation. My preliminarily in vivo data show that miR-XYZ reduces tumor xenografttumor growth and abolishes the teratogenic effect of DEX. I conclude that miR-XYZ is a tumor suppressor gene that inhibits EMT by regulating oncogenes and/or genes that control EMT, and DEX is able to activate EMT by suppressing miR-XYZ.

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/content/papers/10.5339/qfarc.2016.HBSP3195
2016-03-21
2019-11-16
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http://instance.metastore.ingenta.com/content/papers/10.5339/qfarc.2016.HBSP3195
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