Endometrial cancer was originally classified according to a dualistic model. More recently, this model has been challenged because tumors seen in daily practice occasionally show overlapping or combined morpho logic and molecular characteristics of both classification types or exhibit ambiguous following website features. In endometrial cancer, myometrial invasion and lymph node metastasis are considered the most important prognostic factors. For these processes to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition. Neurotrophic receptor tyrosine kinase B has been shown to be a key regulator of oncogenesis and tumor progression in various human cancer types including can cer of the lungs and breast. We have also previously demonstrated a novel role of TrkB in promoting EMT and resistance to anoikis.

As an additional receptor tyrosine kinase, TrkB activates diverse downstream signaling cas cades that ultimately induce cellular proliferation and pro survival mechanisms through the AKT, STAT3 and MAPK signaling pathways. MicroRNAs are small non coding ribonucleic acids of approximately 22 bp that Inhibitors,Modulators,Libraries induce RNA interference by base pairing Inhibitors,Modulators,Libraries with the 3 untranslated region of a complementary messenger RNA, which triggers either mRNA translational repression or RNA degradation. Approximately 20 30% of all genes are targeted by miRNAs, and a single miRNA may target as many as 200 genes. In human cancers, specific miRNAs are expressed in different tissues, and changes in the Inhibitors,Modulators,Libraries regulation of gene expression have been associated with carcinogenesis, including endomet rial cancer.

Furthermore, miRNAs cooperatively function with certain Inhibitors,Modulators,Libraries transcription factors in the regula tion of mutual sets of target genes, allowing coordinated modulation of gene expression both transcriptionally and posttranscriptionally. Specifically, a recurring network motif has been revealed in which a transcription factor regulates a miRNA with which it cooperates in regulating a common set of targets. These observations prompted us to hypothesize that specific miRNAs may Inhibitors,Modulators,Libraries control TrkB expression posttranscriptionally in endometrial cancer progression. Here, we report the identification of a set of miRNAs repressed by TrkB in two endometrial cancer cell lines by comprehensive miRNA profiling. One candidate miRNA of interest, miR 204 5p, is located at the cancer associated genomic region 9q21.

1 q22. 3 locus and is known to be significantly dysregulated in broad tumor types, including breast, prostate, and kidney cancers, suggesting a role for miR 204 5p as a tumor suppressor gene. We demon strate a role for miR 204 5p in endometrial cancer and also shed light on a novel posttranscriptional regulatory circuit in which TrkB induces the activation of STAT3 to regulate the expression www.selleckchem.com/products/pazopanib.html of miR 204 5p, which in turn, dir ectly modulates TrkB expression in endometrial cancer cells.