Sox9 and Hif-2α regulate TUBB3 gene expression and affect ovarian cancer aggressiveness

摘要: Abstract SOX9 [(sex determining region Y)-box9] gene has been implicated in the development and progression of different neoplasms. This study investigated role Sox9 expression TUBB3 gene, a marker aggressiveness ovarian cancer (OC), encoding βIII-tubulin protein. Gene was assessed by quantitative polymerase chain reaction (qPCR) OC models. Using chromatin immunoprecipitation (ChIP) we found that engages promoter at minus 980 base pairs from transcriptional start site with enhancing effects. Furthermore is downstream target Hif-2α, transcription factor encoded endothelial PAS domain protein-1 (EPAS1). Hypoxic microenvironment common feature solid tumors associated aggressiveness. In present work knockdown either or EPAS1 abolished induction hypoxia. phenomenon decrease number cell colonies capable growing an anchorage-independent way. nanofluidic genetic analyzer, SOX9, evaluated 182 specimens. Double staining immunohistochemistry employed to evaluate prognostic both βIII-tubulin. Results obtained cellular models matched pattern clinical We documented direct correlation among EPAS1, mRNA level. Patients displaying no for three genes had best outcome. A poor prognosis significant multivariate analysis visible patients featuring high nuclear Sox9. Conclusions allows survival cells upon hypoxic condition, through activation its aberrant prominent aggressive OC.