Transcriptional and Epigenetic Regulation of KIF14 Overexpression in Ovarian Cancer

摘要: KIF14 (kinesin family member 14) is a mitotic kinesin and an important oncogene in several cancers. Tumor expression levels are independently predictive of poor outcome, cancer cells can modulate metastatic behavior by maintaining appropriate cell adhesion migration proteins at the membrane. Thus exciting potential therapeutic target. Understanding KIF14's regulation crucial to development effective selective therapies block its tumorigenic function(s). We previously determined that close 30% serous ovarian cancers (OvCa tumors) exhibit low-level genomic gain, indicating one mechanism overexpression tumors. now report on transcriptional epigenetic KIF14. Through promoter deletion analyses, we identified cis-regulatory region containing binding sites for Sp1, HSF1 YY1. siRNA-mediated knockdown these transcription factors demonstrated endogenous Sp1 YY1, but not HSF1. ChIP experiments confirmed enrichment both YY1 OvCa lines with high expression. A strong correlation was seen primary tumors between expression, further evidence players overexpression. Hypomethylation patterns were observed tumors, suggesting minor role methylation control gene miRNA analysis miR-93, miR-144 miR-382 had significantly lower than normal tissues; treatment line mimics inhibitors specifically modulated mRNA levels, pointing novel mechanisms Our findings reveal multiple upregulation cells, offering new targets interventions reduce aiming improved prognosis.