Unknown

Dataset Information

0

Induction of the transcriptional repressor ZBTB4 in prostate cancer cells by drug-induced targeting of microRNA-17-92/106b-25 clusters.


ABSTRACT: Androgen-insensitive DU145 and PC3 human prostate cancer cells express high levels of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4, and treatment of cells with methyl 2-cyano-3,11-dioxo-18?-olean-1,12-dien-30-oate (CDODA-Me) inhibited cell growth and downregulated Sp1, Sp3, and Sp4 expression. CDODA-Me (15 mg/kg/d) was a potent inhibitor of tumor growth in a mouse xenograft model (PC3 cells) and also decreased expression of Sp transcription factors in tumors. CDODA-Me-mediated downregulation of Sp1, Sp3, and Sp4 was due to induction of the transcriptional repressor ZBTB4, which competitively binds and displaces Sp transcription factors from GC-rich sites in Sp1-, Sp3-, Sp4-, and Sp-regulated gene promoters. ZBTB4 levels are relatively low in DU145 and PC3 cells due to suppression by miR paralogs that are members of the miR-17-92 (miR-20a/17-5p) and miR-106b-25 (miR-106b/93) clusters. Examination of publically available prostate cancer patient array data showed an inverse relationship between ZBTB4 and miRs-20a/17-5p/106b/93 expression, and increased ZBTB4 in patients with prostate cancer was a prognostic factor for increased survival. CDODA-Me induces ZBTB4 in prostate cancer cells through disruption of miR-ZBTB4 interactions, and this results in downregulation of pro-oncogenic Sp transcription factors and Sp-regulated genes.

SUBMITTER: Kim K 

PROVIDER: S-EPMC3632183 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3324448 | BioStudies
2012-01-01 | S-EPMC3288192 | BioStudies
2012-01-01 | S-EPMC3522018 | BioStudies
2014-01-01 | S-EPMC4309261 | BioStudies
2014-01-01 | S-EPMC4054319 | BioStudies
2017-01-01 | S-EPMC6357769 | BioStudies
2017-01-01 | S-EPMC5222719 | BioStudies
2019-01-01 | S-EPMC6397684 | BioStudies
2012-01-01 | S-EPMC4924623 | BioStudies
1000-01-01 | S-EPMC3845888 | BioStudies