BackgroundBladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1) on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism.MethodsThe levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.ResultsThe levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells.ConclusionDownregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt/β-catenin pathway.

Protein disulfide isomerases A6 (PDIA6) belongs to the PDI family. Recently, PDIA6 was found to have a close association with various cancers. However, there has been little investigation into the biological functions of PDIA6 in bladder cancer (BC). In this study, we explored the expression pattern and functional significance of PDIA6 in BC. We found that PDIA6 was overexpressed in BC tissues and cell lines. The in vitro study showed that PDIA6 downregulation significantly inhibited BC proliferation and invasion. In addition, the in vivo experiment demonstrated that PDIA6 downregulation decreased the volume, weight, and metastasis of tumors. Furthermore, PDIA6 downregulation reduced the protein expression of β-catenin, cyclin D1, and c-Myc and thus suppressed the Wnt/β-catenin signaling pathway. In conclusion, we suggest that PDIA6 could be targeted for the treatment of BC.

BackgroundRenal cell carcinoma (RCC) is the most common cancer in kidney malignancies. UCA1 has been identified as an oncogenic lncRNA in multiple cancers, including RCC. However, the underlying molecular mechanism of UCA1 involved in RCC progression is far from being addressed.MethodsReverse-transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure expressions of UCA1, miR129, and SOX4 mRNA. Western blot assays were employed to detect SOX4 protein expression. Cell proliferation, invasion, and apoptosis were assessed by CCK-8, Matrigel invasion, and annexin–fluorescein isothiocyanate (FITC) apoptosis-detection assays, respectively. The interaction between UCA1 and miR129 was demonstrated by luciferase, RNA pull-down, and RNA-immunoprecipitation (RIP) assays. Luciferase assays were also used to explore whether UCA1 was able to act as a molecular sponge of miR129 to affect the interplay of miR129 and SOX4.ResultsUCA1 expression was upregulated in RCC tissue and cells, and higher UCA1 expression was associated with advanced pathogenic status and poor prognosis of RCC patients. UCA1 knockdown suppressed proliferation and invasion and induced apoptosis in RCC cells. UCA1 inhibited miR129 expression by direct interaction in RCC cells. miR129 overexpression inhibited cell proliferation and invasion and promoted apoptosis. Moreover, miR129 downregulation abrogated UCA1 knockdown-mediated antiproliferation, anti-invasion, and proapoptosis effects in RCC cells. Furthermore, UCA1 acted as a ceRNA of miR129 to enhance target-gene SOX4 expression in RCC cells.ConclusionUCA1 promoted cell proliferation and invasion and inhibited apoptosis by regulating SOX4 via miR129 in RCC, offering a promising therapeutic target and prognosis marker for RCC patients.

Background Taurine-upregulated gene 1 ( TUG1 ) has been documented to be implicated in carcinogenesis and chemoresistance in solid tumors. Here, we explored the biological role and regulatory mechanism of TUG1 in progression and chemoresistance of urothelial carcinoma of the bladder (UCB). Methods Nuclear factor-erythroid 2 ( NF-E2 ) -related factor 2 ( Nrf2 ) mRNA and TUG1 expression was determined by quantitative reverse transcription polymerase chain reaction. Western blot was performed to determine the protein levels of Nrf2, p-glycoprotein (p-gp), Ki-67 (Ki67), matrix metalloproteinase (MMP)-2 and MMP-9 and cleaved caspase-3. The effects of either Nrf2 or TUG1 knockdown on the proliferation, invasion, apoptosis and adriamycin (ADM) resistance of UCB cells were evaluated by CCK-8 assay, transwell invasion assay and flow cytometry analysis. Xenograft tumor assay was carried out to confirm the role of Nrf2 and TUG1 in ADM resistance of UCB cells in vivo. Results Nrf2 and TUG1 were upregulated in UCB tissues and cell lines. A positive correlation between Nrf2 and TUG1 expression was discovered in UCB tissues. Moreover, Nrf2 and TUG1 expression levels were higher in ADM-resistant cells compared with those in parental cells. Furthermore, Nrf2 positively regulated the expression of TUG1 in UCB cells. Knockdown of either Nrf2 or TUG1 led to the inhibition of cell proliferation and invasion and promotion of cell apoptosis, accompanying with down-regulation of Ki67, MMP-2 and MMP-9 and up-regulation of cleaved caspase-3. Knockdown of either Nrf2 or TUG1 enhanced the sensitivity of BIU-87/ADM and T24/ADM cells to ADM, as indicated by decreased expression of p-gp. Besides, knockdown of either Nrf2 or TUG1 inhibited tumor growth in the absence or presence of ADM in vivo. Conclusions Nrf2 induces the up-regulation of TUG1 to promote progression and ADM resistance in UCB.

Aim: In the present study, we investigate the expression of caldesmon (CAD) isoforms in rabbit detrusor smooth muscles (DSM) during the progression of partial bladder outlet obstruction and relate them with the time course of obstruction. Methods: Detrusor samples were obtained from the bladders of rabbits with partial bladder outlet obstruction and sham-operated control rabbits after 1, 2, 4, and 8 weeks of obstruction. Contractile responses to field stimulation and carbachol were determined in the isolated bladder strips. Western blotting was used to determine the relative levels of CaD isoform expression at the protein levels. Results: The contractile responses decreased progressively over the course of obstruction. The expression of l-CaD increased significantly to approximately the same extent as the 1-4-week obstructed groups and further in the 8-week obstructed group. The expression of h-CaD increased in all of the obstructed bladders, but at significantly higher levels in the 1-2-week obstructed bladders compared to the control and 4-8-week obstructed bladders. Conclusions: The changes in the isoforms of CaD may be part of the molecular mechanism for bladder compensation following partial bladder outlet obstruction. The overexpression of l-CaD and the h-CaD/l-CaD ratio could be markers for the status of DSM remodeling and dysfunction. Key wordsbladder; obstruction; h-caldesmon; l-caldesmon; contractility 1 Correspondence to Prof Da-lin HE. P h n 86 -2 9-8 53 2-3 94 5. Fax 86 -2 9-8 52 5-1 63 2.