Induction of the Transcriptional Repressor ZBTB4 in Prostate Cancer Cells by Drug-induced Targeting of microRNA-17-92/106b-25 Clusters
作者： KyoungHyun Kim , Gayathri Chadalapaka , Satya S Pathi , Un-Ho Jin , Ju-Seog Lee
DOI: 10.1158/1535-7163.MCT-12-0181
关键词:
摘要: Androgen-insensitive DU145 and PC3 human prostate cancer cells express high levels of specificity protein (Sp) transcription factors Sp1, Sp3 Sp4, treatment with methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) inhibited cell growth downregulated Sp4 expression. CDODA-Me (15 mg/kg/d) was a potent inhibitor tumor in mouse xenograft model (PC3 cells) also decreased expression Sp tumors. CDODA-Me-mediated downregulation due to induction the transcriptional repressor ZBTB4 which competitively binds displaces from GC-rich sites Sp3, Sp-regulated gene promoters. are relatively low suppression by microRNA (miR) paralogs that members miR-17-92 (miR-20a/17-5p) miR-106b-25 (miR-106b/93) clusters. Examination publically available patient array data showed an inverse relationship between miRs-20a/17-5p/106b/93 expression, increased patients prognostic factor for survival. induces through disruption miR-ZBTB4 interactions this results pro-oncogenic genes.
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