ABSTRACT
PURPOSE: Bladder cancer is one of the most frequent carcinomas worldwide, the incidence of which ranks fourth in males. MiR-19a is identified as one of the key miRs associated with tumorigenesis and has been documented to act as an oncogene in various types of tumors. The aim of this study was to explore the effects of miR-19a and RhoB in bladder cancer. METHODS: The expression of miR-19a was analyzed from 54 paired of bladder cancer and paracancer tissues by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell assay was employed to confirm the invasion capacity in bladder cancer. Dual luciferase reporter assay was utilized to analyze the association between the expression of miR-19a and RhoB. Western blot analyses were performed to detect the relative protein expression. RESULTS: miR-19a was clearly overexpressed in bladder cancer tissues and cells, while the expression of RhoB was lower in bladder cancer tissues and cells as compared with corresponding paracancer tissues and normal bladder cells. Also, miR-19a could promote the invasion and epithelial-mesenchymal transition (EMT) of bladder cancer cells through inhibiting the expression of RhoB. Moreover RhoB was identified as a direct target of miR-19a and the inverse relationship between them was also observed. CONCLUSIONS: This data demonstrated that miR-19a promoted the invasion and EMT through targeting RhoB. It is suggested that miR-19a/RhoB axis may show a new way for the treatment of bladder cancer.
Subject(s)
MicroRNAs/genetics , Neoplasm Invasiveness/genetics , Urinary Bladder Neoplasms/genetics , rhoB GTP-Binding Protein/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Neoplasm Invasiveness/pathology , Neoplasm Staging , Urinary Bladder Neoplasms/pathologyABSTRACT
Altered expression of long non-coding RNAs (lncRNAs) has been reported in many malignancies, including prostate cancer. However, the role of lncRNA MNX1-AS1 in prostate cancer has not been reported. Here, we report that MNX1-AS1 is expressed in prostate cancer tissues and cells and that siRNA-mediated knockdown of MNX1-AS1 inhibits proliferation, migration, and invasion of prostate cancer DU145 and PC3 cells. In addition, down-regulation of MNX1-AS1 decreased expression of proliferating cell nuclear antigen, PH-3, N-cadherin, and vimentin, but enhanced expression of E-cadherin. In conclusion, this is the first report that knockdown of MNX1-AS1 suppresses prostate cancer cell proliferation, migration, and invasion. We believe that MNX1-AS1 may be a potential new therapeutic target for prostate cancer patients.
Subject(s)
Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Homeodomain Proteins/genetics , Neoplasm Invasiveness/genetics , Prostatic Neoplasms/genetics , Transcription Factors/genetics , Down-Regulation , Gene Knockdown Techniques , Homeodomain Proteins/metabolism , Humans , Male , PC-3 Cells , Transcription Factors/metabolismABSTRACT
Prostate cancer gene expression marker 1 (PCGEM1) is a prostatespecific gene overexpressed in prostate cancer cells that promotes cell proliferation. To study the molecular mechanism of PCGEM1 function in hormonerefractory prostate cancer, the interaction between myocyte enhancer factor 2 (MEF2) and PCGEM1 was assessed by a luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. In addition, the underlying mechanism of PCGEM1 regulating expression of microRNA (miR)148a in PC3 prostate cancer cells was evaluated. Relative expression levels were measured by reverse transcriptionquantitative polymerase chain reaction, and early apoptosis was measured by flow cytometry. PCGEM1 was demonstrated to be overexpressed in prostate cancer tissues compared with noncancerous tissues. Expression levels of PCGEM1 in PC3 cancer cells were demonstrated to be regulated by MEF2, as PCGME1 mRNA was increased by MEF2 overexpression but decreased by MEF2 silencing. MEF2 was also demonstrated to enhance the activity of PCGEM1 promoter and thus promote PCGEM1 transcription. In addition, downregulation of PCGEM1 expression in PC3 cells increased expression of miR148a. By contrast, overexpression of PCGEM1 decreased miR148a expression. Finally, PCGME1 silencing by small interfering RNA significantly induced early cell apoptosis but this effect was reduced by a miR148a inhibitor. In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development.
