ABSTRACT
Purpose: Bladder cancer (BCa) is a common malignancy in the urinary system. This study aims to explore the role of miR-186 in BCa tumorigenesis. Methods: The expression of miR-186 and ADAMTS12 in clinical BCa tissues and cell lines was detected. BCa cell lines T24, 5637 and EJ were used to transfect miR-186 mimics or inhibitors. Luciferase reporter gene detection confirmed the correlation between miR-186 and ADAMTS12. MTT method and flow cytometry were used to detect cell viability and apoptosis. Cell migration and invasion ability was detected by transwell assay. The protein level of ADAMTS12, ß-catenin, GSK-3ß and p-GSK-3ß was determined using western blot analysis. Results: MiR-186 was negatively correlated with the expression of ADAMTS12 in BCa tissues. Further research confirmed that ADAMTS12 is the direct target of miR-186. In addition, overexpression of miR-186 down-regulated the expression of ADAMTS12, inhibiting cell viability and apoptosis, while knockout of miR-186 led to the opposite result. miR-186 also inhibits the phosphorylation of GSK-3 ß and ß-catenin without changing the total GSK-3ß level. Our study shows that miR-186 has a negative regulatory effect on the expression of ADAMTS12 in clinical specimens and in vitro. miR-186 can inhibit the proliferation and invasion of BCa cells. Conclusions: miR-186 has the potential to be used as a biomarker in the early detection of BCa.
Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Humans , beta Catenin/genetics , beta Catenin/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Glycogen Synthase Kinase 3 , Glycogen Synthase Kinase 3 beta/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathologyABSTRACT
The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase9 (MMP9) via targeting of phosphoAKT (pAKT). FASNspecific smallinterfering RNA (FASNsiRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAMconjugated FASNsiRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, pAKT, AKT, and migrationassociated protein MMP9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASNsiRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of pAKT as well as the expression of MMP9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.
Subject(s)
Cell Movement , Down-Regulation , Fatty Acid Synthases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Urinary Bladder Neoplasms/enzymology , Urinary Bladder Neoplasms/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cerulenin/pharmacology , Down-Regulation/drug effects , Gene Knockdown Techniques , Humans , Phosphorylation/drug effects , RNA, Small Interfering/metabolismABSTRACT
BACKGROUND: Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients. METHODS: We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased all-cause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11-1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06-1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03-1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study. CONCLUSION: Our data showed that PBT significantly increased the risks of all-cause mortality, cancer-specific mortality and cancer recurrence in patients undergoing RC for bladder cancer.
Subject(s)
Blood Transfusion/methods , Cystectomy , Perioperative Period , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/therapy , Animals , Humans , Treatment OutcomeABSTRACT
Prostate cancer (PCa) remains the most commonly diagnosed malignant tumor in men, and is the second highest cause of cancer mortality after lung tumors in the United States. Accumulating research indicates that microRNAs (miRNAs) are increasingly being implicated in PCa. miRNAs are conserved small noncoding RNAs that control gene expression posttranscriptionally. Recent profiling research suggests that miRNAs are aberrantly expressed in PCa, and these have been implicated in the regulation of apoptosis, cell cycle, epithelial to mesenchymal transition, PCa stem cells, and androgen receptor pathway. All of these might provide the basis for new approaches for PCa. Here, we review current findings regarding miRNA research in PCa to provide a strong basis for future study aimed at promising contributions of miRNA in PCa.
