title: Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.
abstract: Androgen Receptor (AR) signaling is critically important during the development and progression of prostate cancer (PCa). The AR signaling is also important in the development of castrate resistant prostate cancer (CRPC) where AR is functional even after androgen deprivation therapy (ADT); however, little is known regarding the transcriptional and functional regulation of AR in PCa. Moreover, treatment options for primary PCa for preventing the occurrence of CRPC is limited; therefore, novel strategy for direct inactivation of AR is urgently needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue specimens, especially in patients with higher Gleason grade tumors, consistent with increased expression of AR. Forced over-expression of miR-34a in PCa cell lines led to decreased expression of AR and prostate specific antigen (PSA) as well as the expression of Notch-1, another important target of miR-34a. Most importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy showed reexpression of miR-34a, which was consistent with decreased expression of AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells. These results suggest, for the first time, epigenetic silencing of miR-34a in PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful for the inactivation of AR in the treatment of PCa.[This corrects the article on p. 14 in vol. 4.].
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: D
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: E
authors.initials: E
authors.lastname: Heath
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: M
authors.initials: M
authors.lastname: Cher
authors.affiliation: Department of Urology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: I
authors.initials: I
authors.lastname: Powell
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: L
authors.initials: L
authors.lastname: Heilbrun
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: S
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: S
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: O
authors.initials: O
authors.lastname: Hassan
authors.affiliation: Department of Oncology, Henry Ford Health System Detroit, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Henry Ford Health System Detroit, MI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Department of Pathology, Henry Ford Health System Detroit, MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chitale
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: Wa
authors.initials: W
authors.lastname: Sakr
authors.affiliation: Department of Urology, Henry Ford Health System Detroit, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Menon
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, Michigan.
authors.forename: Fh
authors.initials: F
authors.lastname: Sarkar
keywords: BR-DIM; PSA; androgen receptor (AR); methylation; miR-34a