Identification of miR-133b and RB1CC1 as Independent Predictors for Biochemical Recurrence and Potential Therapeutic Targets for Prostate Cancer

Abstract

Objective: We aimed to investigate the contribution of microRNA-133b (miR-133b) in prostate cancer cell proliferation, cell cycle, and apoptosis. We also examined expression of miR-133b in prostate cancer tissues, and evaluated the prognostic significance of miR-133b, as well as its target gene RB1CC1 in patients with prostate cancer after radical prostatectomy.Experimental Design: miR-133b mimics (miR-133bm) and anti-miR-133b were transfected into LNCaP and PC-3 cells. CCK-8 was used to look at cell proliferation, flow cytometric analysis was carried out to study cell cycle, and apoptosis was determined by caspase-3 activity. miR-133b expression was assessed by real-time reverse transcription PCR and in situ hybridization in prostatic cell lines and 178 prostate tissue samples, respectively. The protein level of RB1CC1 was examined by Western blot and immunohistochemistry in prostatic cell lines and prostate tissue samples, respectively.Results: Overexpression of miR-133b in LNCaP cells boosted cell proliferation and cell-cycle progression, but inhibited apoptosis; in contrast, miR-133bm promoted cell apoptosis, but suppressed cell proliferation and cell-cycle progression in PC-3 cells. In LNCaP cells, silencing of RB1CC1, a target of miR-133b, inhibited cell apoptosis, and promoted cell-cycle progression. Moreover, miR-133b expression was significantly inversely correlated with RB1CC1 expression in prostate cancer tissues. Multivariate Cox analysis indicated that miR-133b and RB1CC1 might be two independent prognostic factors of biochemical recurrence.Conclusions: miR-133b might enhance tumor-promoting properties in less aggressive LNCaP cells, whereas this miR may act as a tumor suppressor in more aggressive PC-3 cells. miR-133b and RB1CC1 were independent prognostic indicators for prostate cancer. Clin Cancer Res; 20(9); 2312-25. Ó2014 AACR.

High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma

“…For cell proliferation assay described previously [64], different cell lines were seeded in 96-well plates (about 2000 cells/well) in sextuple. Cells were allowed to grow for 4 to 5 days and cell proliferation analysis was performed by Cell Counting Kit-8 (CCK-8; Dojindo Laboratories) assay at different time points according to the manufacturer's instructions.…”

“…Cell cycle distribution was analyzed as described previously [64]. Briefly, glioma cells were infected by lentiviruses delivering shRNAs against NMI or LacZ as a negative control, and harvested 4 days later, followed by propidium iodide (10μg/mL) staining in the presence of RNase (10μg/mL) for 30 minutes at 4°C in the dark.…”

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

“…Muscle microRNAs in development and disease [102,106] , metastatic lung tumors [107] , proliferating breast cancer [108] , ERαpositive breast cancer [109] , EEC [110] , NSCLC [85] , TSCC [111,112] , laryngeal SCC [113] , and HNSCC [114] (Table 3). Many of the reports identify reduction in a single myomiR, but in case studies of particular cancers often the different myomiRs have been identified as downregulated, for example in NSCLC tumor samples, miR1 [100] , 133a [85,115] , 133b [85,115] , 206 [107] or miR1/206 [99] have been reported, by implication dysregulation of all of the myomiRs.…”

MiR-133b Promotes Neurite Outgrowth by Targeting RhoA Expression

“…MiR-133b is a commonly dys-regulated miRNA in numerous forms of cancer, including lung cancer, gastrointestinal cancer, and prostate cancer [6,7,8]. It has been reported that miR-133b was also a key regulator of cardiac hypertrophy by targeting RhoA and Cdc42.…”