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Abstract Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy.

Abstract Background The roles of lncRNA PLAC2 in bladder cancer (BC) were explored. Methods The expression of PLAC2 in two types of tissue of BC patients was detected by RT-qPCR and the expression data were compared by paired t test. The 56 patients were staged according to the AJCC criteria, and 12, 15, 15 and 14 cases were classified into stage I-IV, respectively. The expression of TGF-β1 and miR-663 in BC tissues were also detected by RT-qPCR experiments. Results Our data showed that the expression levels of PLAC2 were significantly lower in BC tissues than that in non-cancer tissues. The expression of PLAC2 was not affect by clinical stages and low expression levels of PLAC2 predicted lower survival rate. The expression of PLAC2 was positively correlated with miR-663 and inversely correlated with TGF-β1 in BC tissues. In BC cells, downregulated TGF-β1 and upregulated miR-663 were observed after the overexpression of PLAC2. Overexpression of PLAC2 also resulted in suppressed invasion and migration of BC cells. Overexpression of miR-663 resulted in downregulated TGF-β1 but did not affect the expression of PLAC2. Overexpression of TGF-β1 reduced the inhibitory effects of overexpression of PLAC2 and miR-663 on cell migration and invasion. Conclusion PLAC2 can upregulate miR-663 to downregulate TGF-β1 and suppress BC cell migration and invasion.

Increasing evidence suggests that microRNAs (miRNAs) play critical roles in bladder tumorigenesis and development by combining with the 3’ untranslated regions (3’-UTRs) of the corresponding mRNAs to negatively regulate gene expression. The role of miR-182-5p in bladder cancer (BC) remains unclear. Therefore, this study aimed to clarify the functional role of miR-182-5p in BC. We predicted candidate mRNAs for miR-182-5p via three databases (TarBase, ENCORI, and miRDB). Dual-luciferase reporter assays and target prediction confirmed FOXF2 as a potential target of miR-182-5p. Quantitative RT-PCR (qRT-PCR) showed that endogenous miR-182-5p expression was significantly upregulated in BC cell lines and clinical samples of BC patients. IHC, western blotting, and qRT-PCR assays indicated that FOXF2 expression was concurrently downregulated in BC tissues and BC cell lines. Gain- and loss-of-function studies showed that the overexpression of miR-182-5p enhanced the proliferation and migration of BC cells, while the downregulation of miR-182-5p showed the opposite results. The effects induced by miR-182-5p were attenuated with the restoration of FOXF2 expression. In BC cells, the upregulation of miR-182-5p not only decreased FOXF2 expression but also markedly increased Sonic hedgehog (SHH) pathway levels. These findings suggested that FOXF2 directly binds to miR-182-5p and that miR-182-5p acts as a tumor promoter in BC genesis and metastasis by targeting FOXF2. In addition, miR-182-5p plays a pro-cancer role by downregulating FOXF2 and activating the SHH pathway. [ABSTRACT FROM AUTHOR]

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Background: The roles of lncRNA PLAC2 in bladder cancer (BC) were explored.Methods: The expression of PLAC2 in two types of tissue of BC patients was detected by RT-qPCR and the expression data were compared by paired t test. The 56 patients were staged according to the AJCC criteria, and 12, 15, 15 and 14 cases were classified into stage I-IV, respectively. The expression of TGF-β1 and miR-663 in BC tissues were also detected by RT-qPCR experiments.Results: Our data showed that the expression levels of PLAC2 were significantly lower in BC tissues than that in non-cancer tissues. The expression of PLAC2 was not affect by clinical stages and low expression levels of PLAC2 predicted lower survival rate. The expression of PLAC2 was positively correlated with miR-663 and inversely correlated with TGF-β1 in BC tissues. In BC cells, downregulated TGF-β1 and upregulated miR-663 were observed after the overexpression of PLAC2. Overexpression of PLAC2 also resulted in suppressed invasion and migration of BC cells. Overexpression of miR-663 resulted in downregulated TGF-β1 but did not affect the expression of PLAC2. Overexpression of TGF-β1 reduced the inhibitory effects of overexpression of PLAC2 and miR-663 on cell migration and invasion.Conclusion: PLAC2 can upregulate miR-663 to downregulate TGF-β1 and suppress BC cell migration and invasion. [ABSTRACT FROM AUTHOR]

Bufalin has been demonstrated to possess a wide range of pharmacological effects. Among these is its antitumour effect, which has been confirmed in multiple organs or tissues and provoked many concerns. However, its cytostatic effect and underlying mechanism in bladder cancer has not thoroughly been elucidated. This study aimed to investigate the hypothesis that Bufalin induces cell apoptosis and inhibits cell growth in bladder cancer through the inactivation of Na+/K+‑ATPase (NKA). In the current study, it was demonstrated that Bufalin remarkably inhibited cell viability and induced cell apoptosis in bladder cancer cell line T24. Subsequently, we found that the expression of NKA was significantly supressed in Bufalin‑treated cells and the NKA‑α3 isoform was most sensitive to Bufalin among all α subunits of NKA. By transfection with NKA‑α3 overexpressing plasmids, the expression of the NKA‑α3 subunit was upregulated and NKA‑α3 overexpression was found to markedly attenuated Bufalin‑induced cell apoptosis in T24 cells, suggesting NKA‑α3 played a critical role in Bufalin‑induced cell apoptosis. Taken together, the present study confirmed that Bufalin promotes tumour apoptosis and inhibits tumour growth in bladder cancer in vitro, and this antitumour effect may be ascribed to the inactivation of NKA. [ABSTRACT FROM AUTHOR]

The article reports that BRD4 induces cisplatin resistance in a bladder cancer (BCa) xenograft mouse model. (A) Axillary tumor formation in nude mice. (B) Tumors harvested from each xenograft mouse were photographed. (C) The volume of the xenograft tumor was measured at the indicated time after treatment. (D) Tumor weight of the different treatment groups was calculated posttreatment.