Estrogen Receptor-alpha (Phospho-Ser104) ELISA Kit

Objective MicroRNAs (MiRNAs) is thought to play a critical role in the initiation and progress of ovarian cancer (OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Three mRNA datasets of normal ovarian tissue and OC, GSE18520,GSE14407 and GSE36668, were downloaded from Gene Expression Omnibus (GEO) to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was conducted by STRING and Cytoscape, and the effect of HUB gene on the outcome of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1,MAPK10, Tp53 and the high expression of YKT,NSF were related to poor prognosis of OC. Conclusion Our results indicate that miR-30a is of significance for the biological progress of OC.

The cyclin-dependent kinase 2 (CDK2) inhibitor dinaciclib, a potential anti-cancer drug, has been tested in clinical trials and reported to suppress tumor initiating cells. Our recent study demonstrated that pharmacological inhibition of CDK2 or enhancer of zeste homolog 2 (EZH2) allows re-expression of ER alpha and converts triple-negative breast cancers (TNBC) to luminal ER alpha-positive, rendering TNBC cells targetable by tamoxifen. Like TNBC, EZH2 is also commonly overexpressed in ovarian cancers, and overexpression of cyclin El gene (CCNE1) and/or amplification of its associated kinase CDK2 gene is present in ovarian tumor specimens, both of which are associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). We determined whether inhibition of CDK2-mediated phosphorylation of EZH2 activates ER alpha expression in ER alpha-negative HGSOC cells, rendering them targetable by hormonal therapy. The specific CDK2 inhibitor repressed phosphorylation of EZH2 at T416, and in turn activated the expression of its downstream target ER alpha gene (ESR1). We tested the efficacy of the combination of CDK2 inhibitor and tamoxifen and found significant synergistic inhibition. We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. Our results indicated that the combination treatment of CDK2 inhibitor and tamoxifen has the potential to benefit patients with ER alpha-negative HGSOC.