USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway

Abstract BackgroundBladder cancer is the fourth and tenth most common malignancy in men and women worldwide, respectively. One of the main reasons for the unsatisfactory therapeutic control of bladder cancer is that the molecular biological mechanism of bladder cancer is complex. Gasdermin B (GSDMB) is one member of the gasdermin family and participates in the regulation of cell pyroptosis. The role of GSDMB in bladder cancer has not been studied to date.MethodsThe clinical relevance of GSDMB was examined by the TCGA data set. Functional assays, such as the MTT assay, Celigo fluorescent cell-counting assay, Annexin V-APC assay and xenografts, were used to determine the biological role of GSDMB in bladder cancer. The interaction between GSDMB and STAT3, or GSDMB and USP24 were detected by Mass spectrometry and verified through immunoprecipitation. The relationship between USP24, GSDMB and STAT3 was examined by Western blot analysis and immunohistochemistry.ResultsIn this study, bioinformatics analysis indicated that the mRNA expression level of GSDMB in bladder cancer tissues was higher than that in adjacent normal tissues. Then, we showed that GSDMB promoted bladder cancer progression. Furthermore, we demonstrated that GSDMB interacted with STAT3 to increase the phosphorylation of STAT3 and modulate the glucose metabolism and promote tumor growth in bladder cancer cells. Besides, we also showed that USP24 stabilized GSDMB to activate STAT3 signaling, which was blocked by the USP24 inhibitor. ConclusionsWe suggested that aberrantly up-regulated GSDMB was responsible for enhancing the growth and invasion ability of bladder cancer cells. Then, we showed that GSDMB could bind to STAT3 and activate STAT3 signaling in bladder cancer. Furthermore, we also demonstrated that USP24 interacts with GSDMB and prevents GSDMB from degradation in bladder cancer cells. Therefore, the USP24/GSDMB/STAT3 axis may be a new targetable signaling pathway for bladder cancer treatment.

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Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000491536 ◽

2018 ◽

Vol 47 (6) ◽

pp. 2250-2260 ◽

Cited By ~ 5

Author(s):

Teng Hou ◽

Lijie Zhou ◽

Longwang Wang ◽

Gallina Kazobinka ◽

Yumao Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Akt Pathway ◽

Advanced Tumor Stage ◽

Large Tumor ◽

Advanced Tumor ◽

Bladder Cancer Cells ◽

The Impact

Background/Aims: Leupaxin (LPXN) is a member of the paxillin protein family. Several studies have reported that LPXN regulates cancer development; however, the role of LPXN in bladder cancer remains unknown. Methods: The expression of LPXN in bladder cancer cells and tissues was determined by real-time PCR, western blotting, and immunohistochemistry, respectively. The biological role of LPXN in bladder cancer cell proliferation, invasion, and angiogenesis was explored both in vitro and in vivo. Results: LPXN expression was elevated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. High LPXN expression was correlated with large tumor size, advanced tumor stage, and poor survival in bladder cancer patients. Overexpression of LPXN significantly promoted the proliferation, invasion, and angiogenesis of bladder cancer cells, while suppressing LPXN had the opposite effects. The impact on tumor progression was abolished by inhibiting PI3K/ AKT signaling pathway. We further demonstrated that LPXN probably up-regulated S100P via the PI3K/AKT pathway. Conclusions: LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer.

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Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

BioMed Research International ◽

10.1155/2014/619829 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 98

Author(s):

Carrie A. Franzen ◽

Patricia E. Simms ◽

Adam F. Van Huis ◽

Kimberly E. Foreman ◽

Paul C. Kuo ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Internal Standard ◽

Cancer Recurrence ◽

High Recurrence Rate ◽

Bladder Cancer Cells ◽

Cancer Cell Survival

Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression.

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LINC00958 promotes bladder cancer carcinogenesis by targeting miR-490-3p and AURKA

BMC Cancer ◽

10.1186/s12885-021-08882-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hongtao Zhen ◽

Peng Du ◽

Qiang Yi ◽

Xiaolong Tang ◽

Tongqing Wang

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Treatment Method ◽

Bladder Cancer Cells ◽

Cell Progression ◽

New Treatment ◽

Cancer Tissues ◽

Proliferation And Invasion

Abstract Background Bladder cancer is a prevalent malignancy of the urinary system, in which long non-coding RNAs (lncRNAs) are highly associated. We aimed to elucidate the role of LINC00958 in bladder cancer. Methods LINC00958 expression levels were measured using qRT-PCR. The interaction of LINC00958-miR-490-3p-AURKA was analyzed by luciferase, RIP, and RNA pull-down assays. The biological roles of LINC00958, miR-490-3p, and AURKA in bladder cancer cells were analyzed using CCK8, BrdU, and transwell assays. Results Increased expression of LINC00958 and AURKA was observed in bladder cancer tissues and cell lines. Decreased LINC00958 expression repressed bladder cancer progression and downregulation of miR-490-3p accelerated bladder cancer cell progression. Moreover, LINC00958 sponges miR-490-3p to upregulate AURKA expression, thereby promoting carcinogenesis in bladder cancer cells. Conclusions Our study revealed that LINC00958 facilitated cell proliferation and invasion, and suppressed cell apoptosis by sponging miR-490-3p and upregulating AURKA, thus inspiring a new treatment method for bladder cancer.

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Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells

Open Medicine ◽

10.1515/med-2021-0299 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1010-1021

Author(s):

Jiangbo Zhu ◽

Fei Zhang

Keyword(s):

Bladder Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Progression ◽

Circular Rna ◽

Cell Counting ◽

Luciferase Reporter ◽

Bladder Cancer Cells ◽

Cancer Tissues

Abstract Background Bladder cancer is a common malignancy in the world. It is reported that circular RNA VANGL1 (circ_VANGL1) was involved in bladder cancer progression. However, the functional role and molecular mechanism of circ_VANGL1 in bladder cancer were still unclear. Methods The levels of circ_VANGL1, microRNA-145-5p (miR-145-5p), and Sex-determining region Y-related high-mobility group box 4 (SOX4) in bladder cancer tissues and cells were determined by quantitative real-time polymerase chain (RT-qPCR). The relative protein expression was detected by western blot. Cell counting kit-8 (CCK8) and flow cytometry analysis were used to measure cell viability, IC50 value, and apoptosis rate. The interaction between miR-145-5p and circ_VANGL1 or SOX4 was predicted by online software starBase v2.0 or Targetscan and verified by the dual-luciferase reporter assay. Besides, xenograft mice model was used to detect the effects of circ_VANGL1 in vivo. Results The level of circ_VANGL1 and SOX4 was increased, while miR-145-5p was decreased in bladder cancer tissues and cells. Knockdown of circ_VANGL1 suppressed viability, while promoted apoptosis and increased doxorubicin sensitivity in bladder cancer cells. Moreover, circ_VANGL1 acted as a sponge for miR-145-5p. In addition, miR-145-5p partially reversed the effects of miR-145-5p knockdown in T24 and J82 cells. SOX4 was a target of miR-145-5p and negatively regulated by miR-145-5p. Furthermore, miR-145-5p regulated SOX4 to affect cell progression in bladder cancer cells, including viability, apoptosis, and doxorubicin sensitivity. Besides, circ_VANGL1 suppressed tumor growth and enhanced the doxorubicin sensitivity in bladder cancer in vivo. Conclusion circ_VANGL1 mediated cell viability, apoptosis, and doxorubicin sensitivity by regulating miR-145-5p/SOX4 axis in bladder cancer, providing a potential therapeutic target for bladder cancer therapy.

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792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)34961-9 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 214-215 ◽

Cited By ~ 2

Author(s):

Daniel Cho ◽

Xiao Fang Ha ◽

J. Andre Melendez ◽

Louis J. Giorgi ◽

Badar M. Mian

Keyword(s):

Oxidative Stress ◽

Bladder Cancer ◽

Cancer Cells ◽

Tumorigenic Potential ◽

Bladder Cancer Cells

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Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190206124120 ◽

2019 ◽

Vol 19 (6) ◽

pp. 826-837 ◽

Cited By ~ 3

Author(s):

Pratibha Pandey ◽

Preeti Bajpai ◽

Mohammad H. Siddiqui ◽

Uzma Sayyed ◽

Rohit Tiwari ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Gall Bladder ◽

Cancer Cells ◽

Caspase 3 ◽

Annexin V ◽

Gall Bladder Cancer ◽

Apoptosis Induction ◽

Bladder Cancer Cells ◽

Hoechst Staining

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

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