title: BCL9, a coactivator for Wnt/β-catenin transcription, is targeted by miR-30c and is associated with prostate cancer progression.
abstract: B-cell lymphoma 9 (BCL9), a component of aberrantly activated Wnt signaling, is an important contributing factor to tumor progression. Our previous data indicated that downregulation of the tumor suppressor microRNA-30c (miR-30c) was a frequent pathogenetic event in prostate cancer (PCa). However, a functional link between miR-30c and BCL9/Wnt signaling, and their clinical and pathological significance in PCa, have not been well established. The present study demonstrated that miR-30c serves as a key negative regulator targeting BCL9 transcription in PCa cells. Ectopic expression of miR-30c was associated with reduced expression of Wnt pathway downstream targets, including c-Myc, cluster of differentiation 44 and sex determining region Y-box 9 in DU145 human PCa cells. Examination of clinical prostate specimens revealed higher levels of BCL9 expression in PCa compared with that in benign prostate tissues. After substantiating this finding by patient sample analysis, BCL9 expression or activity was observed to be closely correlated with PCa biochemical recurrence (BCR) and disease progression, whereas it was inversely associated with miR-30c. Furthermore, overexpression of BCL9 in PCa acted cooperatively with miR-30c low expression to predict earlier BCR in PCa. These findings indicate that inhibition of BCL9/Wnt signaling by miR-30c is important in the progression of PCa. Furthermore, the combined analysis of miR-30c and BCL9 may be valuable tool for prediction of BCR in PCa patients following radical prostatectomy.
authors.affiliation: Reproductive Medicine Centre, Huizhou Municipal Central People's Hospital, Huizhou, Guangdong 516001, P.R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Ling
authors.affiliation: Reproductive Medicine Centre, Huizhou Municipal Central People's Hospital, Huizhou, Guangdong 516001, P.R. China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China; Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Luo
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ze-Zhen
authors.initials: ZZ
authors.lastname: Liu
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ying-Ke
authors.initials: YK
authors.lastname: Liang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Guan-Xing
authors.initials: GX
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Fu-Neng
authors.initials: FN
authors.lastname: Jiang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China; Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Wei-DE
authors.initials: WD
authors.lastname: Zhong
keywords: B-cell lymphoma 9; Wnt signaling; biochemical recurrence; microRNA-30c; prostate cancer