Bladder cancer (BC) is one of the most common tumors in the urinary system. Noncoding RNAs are considered to take part in cellular phenotypes and are emerging as diagnostic and prognostic biomarkers of BC. The aim of this study is to investigate the clinical significance of neuroblastoma- associated transcript 1 (NBAT1) gene and its effects on malignant cellular phenotypes in BC. NBAT1 gene was low-expressed in BC tissues and cell lines and its low-expression was related with high pathological grade and metastasis of BC. Upregulation of NBAT1 gene depressed cell viability and invasiveness of KK47 and T24 cells and arrested KK47 and T24 cells at G1 stage. In addition, NBAT1 could target silence the expression of miR-21-5p in RNA-induced silencing complex-dependent manner. KK47 and T24 cells with miR-21-5p knockdown showed reduced cell viability, G1-stage arrest, and depressed invasiveness. MiR-21-5p mediates the regulatory effects of NBAT1 on malignant cellular phenotypes of BC cells. Moreover, SOCS6 gene was a target gene of miR-21-5p, and miR-21-5p modulated malignant cellular phenotypes of KK47 and T24 cells through targeted silencing of SOCS6. In conclusion, low-expression of NBAT1 is associated with the progress and metastasis of BC, and NBAT1 inhibits malignant cellular phenotypes through miR-21-5p/SOCS6 axis in BC. Our findings help to elucidate the tumorigenesis of BC, and future study will provide a novel therapeutic target for BC.

In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

Purpose: Recent studies showed circular RNA (circRNA) played important regulatory roles in tumors, including genesis of chemotherapy resistance. In this study, the role of circHIPK3 on chemotherapy resistance of bladder cancer (BC) will be clarified. Methods: Real-time quantitative PCR was applied to examine the circHIPK3 expression. The gemcitabine sensitivity and cell proliferation viability were analyzed by Cell Counting Kit-8 assay. Double-stained flow cytometry was used to detect the cell apoptosis. Results: In BC tissues and cell lines, the circHIPK3 expression was down-regulated. Its expression had a negative correlation with pathological grade, lymph node metastasis and gemcitabine insensitivity of BC patients. CircHIPK3 was a independent prognostic biomarker for BC patients. The expression of circHIPK3 in T24/gem and J82/gem cell lines (resistant to gemcitabine) was down-regulated significantly. The over-expression of circHIPK3 decreased IC50 of gemcitabine and promoted gemcitabine's cytotoxicity in T24/gem and J82/gem cells. Conclusions: The circHIPK3 is low-expressed in BC and is an independent prognostic biomarker for BC patients. The low-expression of circHIPK3 is associated with the insensitivity to gemcitabine of BC patients, over-expression of circHIPK3 promotes gemcitabine sensitivity in BC.

Objective: To investigate the clinical significance of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS) gene and its effects on Gemcitabine sensitivity in BUC.Materials and Methods: The expression of CDKN2B-AS gene was examined with real-time quantitative PCR. The cell proliferation and the half maximal inhibitory concentration (IC50) of Gemcitabine were detected with enhanced CCK-8 assay. The apoptosis rate was examined using Annexin V-FITC/PI double-staining apoptosis kit. The protein expression was examined with western blotting. The activity of Wnt signaling pathway was examined with TOP/FOP luciferase assay.Results: CDKN2B-AS gene was high-expressed in BUC tissues and J82, T24 cells compared with paracancerous normal urothelial tissues and SV-HUC-1 cells. Furthermore, the high-expression of CDKN2B-AS gene was related with high pathological grade and low Gemcitabine sensitivity of BUC tissues. The expression of CDKN2B-AS gene in Gemcitabine-resistant T24/Gem cells was much higher than that in T24 cells. Knockdown of CDKN2B-AS gene sensitized T24/Gem cells to Gemcitabine, promoted Gemcitabine-induced cytotoxicity. Knockdown of CDKN2B-AS gene inactivated Wnt signaling pathway, and Wnt signaling pathway mediated the effects on Gemcitabine sensitivity induced by CDKN2B-AS knockdown in T24/Gem cells.Conclusion: LncRNA CDKN2B-AS is high-expressed in BUC and related to low Gemcitabine sensitivity of BUC. CDKN2B-AS inhibited Gemcitabine sensitivity through Wnt signaling pathway in BUC.

BackgroundBladder urothelial carcinoma is the most common genitourinary system cancer in China. The objective of this study was to investigate whether the miR-9 can regulate the invasion ability of human bladder transitional cell carcinoma cells by down-regulation of CBX7.Material/MethodsThe expression of miR-9 was detected by quantitative real-time PCR in bladder transitional cell carcinomas (TCC) and normal bladder transitional cell (NBTC) samples. Bioinformatics software was used to predict some potential target genes of miR-9. T24 cells were transfected with pre-miR-9, and the CBX7 protein expression was detected by Western blot. Luciferase activities assay was selected to verify that CBX7 was a direct and specific gene of miR-9. T24 cells were transfected with pcDNA-CBX7, and the expression of CBX7 gene was detected. Then, the transwell assay was used to detect the invasion ability of T24 cells with CBX7 over-expression.ResultsThe expression of miR-9 increased significantly in human TCC specimens compared to that in NBTC specimens. TargetScan and PicTar software programs predicted CBX7 gene was a target gene of miR-9. The pre-miR-9 could up-regulate the miR-9 expression and down-regulate CBX7 protein expression. The luciferase activities assay verified that CBX7 gene was a direct and specific target gene of miR-9. The pcDNA-CBX7 transfection could up-regulate the CBX7 protein expression, and the invasion ability of T24 cells with CBX7 over-expression decreased significantly.ConclusionsAberrantly expressed miR-9 contributes to T24 cells invasion, partly through directly down-regulating CBX7 protein expression in TCC. This miRNA signature offers a new potential therapeutic target for TCC.