MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling cell cycle regulators, and Ets-1-mediated MMP-2 expression

AbstractExtensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle–related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer. Graphical abstract

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Knockdown of long non-coding RNA linc00511 suppresses proliferation and promotes apoptosis of bladder cancer cells via suppressing Wnt/β-catenin signaling pathway

Bioscience Reports ◽

10.1042/bsr20171701 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 12

Author(s):

Jun Li ◽

Yan Li ◽

Fandong Meng ◽

Liye Fu ◽

Chuize Kong

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Signaling Pathway ◽

Noncoding Rna ◽

Migration And Invasion ◽

Cycle Arrest ◽

Bladder Cancer Cells ◽

Cancer Tissues

More and more studies have shown that long non-coding RNAs (lncRNAs) play critical roles in various biological processes of bladder cancer, including proliferation, apoptosis, migration and cell cycle arrest. LncRNA long intergenic noncoding RNA 00511 (linc00511) is one of the lncRNAs highly expressed in bladder cancer tissues and cells. However, little is known about the roles and mechanisms of linc00511 in bladder cancer. Here, we demonstrated that linc00511 was highly expressed in bladder cancer tissues and cells. Linc00511 knockdown could cause the cell proliferation suppression and cell cycle arrest, which were mediated by p18, p21, CDK4, cyclin D1 and phosphorylation Rb. Suppressed linc00511 could induce the apoptosis in T24 and BIU87 cells via activating the caspase pathway. Down-regulation of linc00511 could also suppress the migration and invasion of T24 and BIU87 cells. In addition, we found that the expression of linc00511 was negatively correlated with that of miR-15a-3p in the clinical bladder cancer samples. Further mechanistic studies showed that linc00511 knockdown induced proliferation inhibition, and apoptosis increase might be regulated through suppressing the activities of Wnt/β-catenin signaling pathway. Thus, we revealed that knockdown of linc00511 suppressed the proliferation and promoted apoptosis of bladder cancer cells through suppressing the activities of Wnt/β-catenin signaling pathway. Moreover, we suggested that linc00511 could be a potential therapeutic target and novel biomarker in bladder cancer.

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Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells

PeerJ ◽

10.7717/peerj.9078 ◽

2020 ◽

Vol 8 ◽

pp. e9078

Author(s):

Xin Gao ◽

Xiaohong Wen ◽

Haowei He ◽

Linlin Zheng ◽

Yibo Yang ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cancer Cells ◽

Growth Cycle ◽

The Cancer Genome Atlas ◽

Cell Counting ◽

Migration And Invasion ◽

Mechanism Analysis ◽

Tumour Development ◽

Bladder Cancer Cells

Bladder cancer is a tumour of the urinary system with high mortality, and there is also a great lack of therapeutic targets in the clinic. Cell division cycle associated 8 (CDCA8), an important component of the vertebrate chromosomal passenger complex, is highly expressed in various tumours and promotes tumour development. However, the role of CDCA8 in bladder cancer is not fully understood. This study aimed to reveal the function of CDCA8 in bladder cancer by determining the relationship between CDCA8 expression and proliferation, metastasis and apoptosis of bladder cancer cells. Firstly, we studied the mRNA expression of CDCA8 through the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and analysed the correlation between CDCA8 expression and prognosis of patients with bladder cancer. We also verified CDCA8 expression in bladder cancer tissues by immunohistochemistry. In addition, CDCA8 expression was inhibited in bladder cancer T24 and 5637 cells, and the effects of CDCA8 on the proliferation, migration and invasion of bladder cancer cell lines were investigated using cell counting kit-8, colony formation, cell cycle, apoptosis, wound healing and Transwell invasion assays. Results showed that CDCA8 was highly expressed in bladder cancer compared with normal tissues, and the high CDCA8 expression was significantly correlated with the poor prognosis of patients. Inhibiting CDCA8 expression inhibited the proliferation, migration and invasion of T24 and 5637 cells and induced the apoptosis of bladder cancer cells. CDCA8 was involved in the regulation of the growth cycle of bladder cancer cells. Bioinformatics-based mechanism analysis revealed that high CDCA8 expression may affect the cell cycle and P53 signalling pathways. In conclusion, our results suggest that CDCA8 is highly expressed in bladder cancer and can promote tumour development. Hence, CDCA8 may serve as an effective therapeutic target for treatment of bladder cancer.

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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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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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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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Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential

Molecules ◽

10.3390/molecules26051381 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1381

Author(s):

So Young Kim ◽

Hyun Hwangbo ◽

Min Yeong Kim ◽

Seon Yeong Ji ◽

Da Hye Kim ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Human Bladder Cancer ◽

Human Bladder ◽

Cycle Arrest ◽

Bladder Cancer Cells ◽

Induced Apoptosis ◽

Human Bladder Cancer Cells

Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells.

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Parthenolide Induces Apoptosis and Cell Cycle Arrest of Human 5637 Bladder Cancer Cells In Vitro

Molecules ◽

10.3390/molecules16086758 ◽

2011 ◽

Vol 16 (8) ◽

pp. 6758-6768 ◽

Cited By ~ 24

Author(s):

Guang Cheng ◽

Liping Xie

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cycle Arrest ◽

Bladder Cancer Cells

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Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway

Nutrients ◽

10.3390/nu14020369 ◽

2022 ◽

Vol 14 (2) ◽

pp. 369

Author(s):

Jochen Rutz ◽

Sebastian Maxeiner ◽

Eva Juengel ◽

Felix K.-H. Chun ◽

Igor Tsaur ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cancer Cells ◽

Olive Mill Wastewater ◽

Mtor Signaling ◽

Beneficial Effects ◽

Cycle Arrest ◽

Bladder Cancer Cells ◽

Olive Mill

Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy.

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