Expression of transcription factor SALL4 in bladder urothelial carcinoma and its relationship with epithelial mesenchymal transformation

Mapping Intimacies ◽

10.21203/rs.3.rs-1195553/v1 ◽

2021 ◽

Author(s):

Wenmin Zhang

Keyword(s):

Bladder Cancer ◽

Transcription Factor ◽

Protein Expression ◽

Urothelial Carcinoma ◽

Cancer Cells ◽

Poor Prognosis ◽

Migration And Invasion ◽

Bladder Urothelial Carcinoma ◽

Bladder Cancer Cells ◽

Mesenchymal Transformation

Abstract Purpose To evaluate the expression levels of spalt-like transcription factor 4 (SALL4) in bladder urothelial carcinoma, and determine its role and underlying mechanism of action in mediating the proliferation, migration and invasion of bladder cancer cells. Methods SALL4 expression was examined in 170 bladder patient urothelial carcinoma tissue samples by immunohistochemistry. Using a SALL4 overexpression plasmid and siRNA-SALL4, the effects of overexpressing and silencing SALL4 on the proliferation, migration and invasion of T24 and 5637 bladder cancer cells was examined using CCK8, migration and invasion assays. Western blot analysis was performed to detect epithelial mesenchymal transition (EMT)-related protein expression. Results The expression rate of SALL4 in low-grade and high-grade urothelial carcinomas was found to be 10% and 49.12%, respectively (P < 0.001), while SALL4 expression was not observed in the normal urothelium. SALL4 protein expression was positively correlated with histological grade, depth of invasion, lymphatic metastasis and vascular invasion of bladder urothelial carcinoma (P < 0.05). In addition, a shorter overall survival time and poor prognosis was observed in the SALL4 protein expression group. Overexpression of SALL4 led to significantly increased cell proliferation, migration and invasion, while knockdown of SALL4 had the opposite effect. In the SALL4 overexpression group, N-cadherin, vimentin, Snail and β-catenin expression were significantly increased, while E-cadherin expression was significantly decreased (P < 0.05). Promotion of EMT was also observed in SALL4-overexpressing cells. In contrast, in the SALL4-siRNA-treated group, EMT was reversed and β-catenin expression was reduced. Conclusions Our data show that the SALL4 gene is associated with the proliferation, invasion and poor prognosis of bladder urothelial carcinoma, and may mediate its effects via the Wnt/β-catenin signaling pathway, which regulates the EMT pathway. Thus, down-regulation of SALL4 may provide a novel therapeutic strategy for the treatment of bladder urothelial carcinoma.

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The role of HIF-1α in regulating NLRP3 inflammasome activation in bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17028 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17028-e17028 ◽

Cited By ~ 1

Author(s):

Yuan-Ru Chen ◽

Hsin-Chih Yeh ◽

Fang-Yen Chiu ◽

Hsin-En Wu ◽

Huei-Chen Fang ◽

...

Keyword(s):

Bladder Cancer ◽

Urothelial Carcinoma ◽

Cancer Cells ◽

Nlrp3 Inflammasome ◽

Migration And Invasion ◽

Inflammasome Activation ◽

T24 Cells ◽

Nlrp3 Inflammasome Activation ◽

Bladder Cancer Cells

e17028 Background: Bladder cancer is one of the most common malignancies of urinary system with the forth incidence rate and the eighth leading mortality rate in male genitourinary tumors. Hypoxia environment activates the hypoxia‐signalling pathway, principally via hypoxia‐inducible transcription factors (HIF) to activate numerous target genes which mediate embryonic vascularization, metabolism, tumor angiogenesis and the other processes to supply tissues with blood and oxygen. Inflammasomes are multiprotein signal responsible for the maturation of proinflammatory cytokines IL-1β and IL-18 as well as trigger the inflammatory cell pyroptosis. Recent study showed that HIF-1α promotes NLRP3 inflammasome activation in bleomycin-induced acute lung injury. However, the role of HIF1α in regulating the progression of bladder cancer has not been examined so far. The present study aimed to investigate the effect of HIF-1α on NLRP3 inflammasome activation in urothelial carcinoma. Methods: In this research, urothelial carcinoma cell lines were treated with NLRP3 inflammasome inducers, LPS/ATP, to induce NLRP3 inflammasome activation. Results: Our preliminary results showed that both T24 and 5637 bladder cancer cells can be induced NLRP3 inflammasome activation and IL-1β secretion. In addition, hypoxia also induces the secretion of IL-1β in T24 cells. We further investigated the effect of NLRP3 inflammasome activation in modulating EMT-related protein levels, migration and invasion in bladder cancer T24 cells. Our results demonstrated that NLRP3 inflammasome activation promotes tumor growth and metastasis in bladder cancer cells. Furthermore, knockdown of HIF1α reduces both inflammatory response and migratory activity in bladder cancer. Conclusions: Collectively, these results suggest that targeting NLRP3 inflammasome might offer potential to treat hypoxic malignant tumor in bladder carcinoma.

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723: Chemokine Receptor CXCR4 Mediates Migration and Invasion of Bladder Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)37972-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 192-192 ◽

Cited By ~ 2

Author(s):

Margitta Retz ◽

Sukhvinder S. Sidhu ◽

Gregory M. Dolganov ◽

Jan Lehmann ◽

Peter R. Carroll ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Chemokine Receptor ◽

Migration And Invasion ◽

Chemokine Receptor Cxcr4 ◽

Bladder Cancer Cells

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Study of LBHD1 Expression with Invasion and Migration of Bladder Cancer

Open Life Sciences ◽

10.1515/biol-2019-0049 ◽

2019 ◽

Vol 14 (1) ◽

pp. 440-447

Author(s):

Chunhui Dong ◽

Yihui Liu ◽

Guiping Yu ◽

Xu Li ◽

Ling Chen

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Tumor Antigens ◽

Urinary Bladder Cancer ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Bladder Cancer Cells

AbstractLBHD1 (C11ORF48) is one of the ten potential tumor antigens identified by immunoscreening the urinary bladder cancer cDNA library in our previous study. We suspect that its expression is associated with human bladder cancer. However, the exact correlation remains unclear. To address the potential functional relationship between LBHD1 and bladder cancer, we examined the LBHD1 expression at the mRNA and protein level in 5 different bladder cancer cell lines: J82, T24, 253J, 5637, and BLZ-211. LBHD1 high and low expressing cells were used to investigate the migration, invasion, and proliferation of bladder cancer cells following transfection of LBHD1 with siRNA and plasmids, respectively. Our experiment showed that the degree of gene expression was positively related to the migration and invasion of the cancer cells while it had little effect on cell proliferation. Knocking down LBHD1 expression with LBHD1 siRNA significantly attenuated cell migration and invasion in cultured bladder cancer cells, and overexpressing LBHD1 with LBHD1 cDNA plasmids exacerbated cell migration and invasion. Nevertheless, a difference in cell proliferation after transfection of LBHD1 siRNA and LBHD1 cDNA plasmids was not found. Our findings suggest that LBHD1 might play a role in cell migration and invasion.

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Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3β/β-catenin pathway

Chemico-Biological Interactions ◽

10.1016/j.cbi.2021.109366 ◽

2021 ◽

Vol 337 ◽

pp. 109366

Author(s):

XiaoJuan Xie ◽

HuiJin Li ◽

JingJing Pan ◽

Xi Han

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Migration And Invasion ◽

Bladder Cancer Cells

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Polyporus polysaccharide regulates proliferation, apoptosis and migration of bladder cancer cells by polarizing macrophages to M1 subtype in tumor microenvironment

10.21203/rs.3.rs-31455/v4 ◽

2020 ◽

Author(s):

Wenyu Jia ◽

Siwan Luo ◽

Gena Lai ◽

Shiqi Li ◽

Shuai Huo ◽

...

Keyword(s):

Flow Cytometry ◽

Bladder Cancer ◽

Western Blot ◽

Cancer Cells ◽

Activated Macrophages ◽

Tnf Α ◽

Bladder Cancer Cells ◽

And Migration ◽

Mesenchymal Transformation ◽

M1 Type

Abstract BackgroundPolyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of PPS activated macrophages in the treatment of bladder cancer.Methods100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Flow cytometry was used to detect the expression of CD14 and CD68 to verify the establishment of macrophage model. After that, Macrophages derived from THP-1 were treated with different concentrations of PPS (1,10 and 100 ug/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with PPS. The conditioned medium from PPS-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2¢-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein.ResultsPPS promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. The results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial–mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. ConclusionThe findings indicated that PPS inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.

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