scholarly journals Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis

2021 ◽  
Author(s):  
Shuilian Wu ◽  
Jialei Yang ◽  
Haotian Xu ◽  
Xin Wang ◽  
Ruirui Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Multiple Tumor ◽  
Bladder Cancer Cells

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

scholarly journals The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinan Guo ◽  
Zhixin Chen ◽  
Hongtao Jiang ◽  
Zhou Yu ◽  
Junming Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Bladder Cancer Cell ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Abstract Background Bladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression. Methods Gene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model. Results Our results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues. Conclusion Collectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.Methods: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.Results: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion: This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer 

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.Methods: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.Results: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion: This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
W. Wang ◽  
J. Qiu ◽  
P. Qu ◽  
H. Chen ◽  
J. Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Positive Association ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer. Methods This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry. Results ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

scholarly journals Regulator of Cullins-1 (ROC1) Negatively Regulates the Gli2 Regulator SUFU to Activate the Hedgehog Pathway in Bladder Cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Malignant Progression ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background: The regulator of cullins-1 (ROC1) is an essential subunit in the Cullin-RING ligase (CRL) protein complex and was shown to be critical in bladder cancer cell survival and malignant progression. This study aimed to explore the regulatory mechanism of ROC1 in bladder cancer malignant progression. Methods: This study explored the underlying mechanisms using both in vitro and in vivo experiments. The expression of the components of Sonic Hedgehog (SHH) pathway was determined by western blotting analysis. ROC1 expression in human tumours was evaluated by immunohistochemical analysis. Results: The data showed that ROC1 overexpression promoted growth of bladder cancer cells, whereas knockdown of ROC1 expression had an opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target SUFU for ubiquitin-dependent degradation, allowing the Gli2 release from the SUFU complex to activate SHH pathway. Furthermore, knockdown of SUFU expression partially rescue the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. At ex vivo, tissue microarray analysis of human bladder cancer specimens revealed an positive association of ROC1 expression with the SHH pathway activity. Conclusion: The current study demonstrated the dysregulation of ROC1-SUFU-GLI2 axis played an important role in bladder cancer progression and targeting of ROC1 expression is warranted further investigation as a novel strategy for future control of bladder cancer.

scholarly journals miR-1-3p Contributes to Cell Proliferation and Invasion by Targeting Glutaminase in Bladder Cancer Cells

2018 ◽  
Vol 51 (2) ◽  
pp. 513-527 ◽  
Author(s):  
Junfeng Zhang ◽  
Longsheng Wang ◽  
Shiyu Mao ◽  
Mengnan Liu ◽  
Wentao Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Methylation Status ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Bladder Cancer Cells ◽  
Cancer Tissues

Background/Aims: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. Methods: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qRT-PCR. Bisulfite sequencing PCR was used for DNA methylation analysis. The target of miR-1-3p was validated by a dual luciferase reporter assay, and the effects of miR-1-3p on phenotypic changes in bladder cancer cells were investigated in vitro and in vivo. Results: The expression of miR-1-3p in bladder cancer cells was downregulated as compared to normal SV-HUC-1 cells. Also, the expression of miR-1-3p was significantly lower in bladder cancer tissues than the corresponding non-cancerous tissues. The methylation status of CpG islands was involved in the regulation of miR-1-3p expression. miR-1-3p inhibited the bladder cancer cell proliferation, migration, and invasion by directly targeting the 3’-UTR of glutaminase. It also exerted an anti-tumor effect by negatively regulating the glutaminase in a xenograft mouse model. Furthermore, GLS depletion resulted in the prolonged expression of γH2AX. Conclusion: Taken together, these results demonstrated that miR-1-3p acts as a tumor suppressor via regulation of glutaminase expression in bladder cancer progression, and miR-1-3p might represent a novel therapeutic target for the treatment of bladder cancer.

scholarly journals Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer

2020 ◽  
Author(s):  
Wei Wang ◽  
Jianxin Qiu ◽  
Pin Qu ◽  
Hui Chen ◽  
Jianyun Lan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Malignant Progression ◽  
Shh Pathway ◽  
Bladder Cancer Cells

Abstract Background The regulator of cullins-1 (ROC1) is an essential subunit in the Cullin-RING ligase (CRL) protein complex and was shown to be critical in bladder cancer cell survival and malignant progression. This study aimed to explore the regulatory mechanism of ROC1 in bladder cancer malignant progression. Methods This study explored the underlying mechanisms using both in vitro and in vivo experiments. The expression of the components of Sonic Hedgehog (SHH) pathway was determined by western blotting analysis. ROC1 expression in human tumours was evaluated by immunohistochemical analysis. Results The data showed that ROC1 overexpression promoted growth of bladder cancer cells, whereas knockdown of ROC1 expression had an opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target SUFU for ubiquitin-dependent degradation, allowing the Gli2 release from the SUFU complex to activate SHH pathway. Furthermore, knockdown of SUFU expression partially rescue the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. At ex vivo, tissue microarray analysis of human bladder cancer specimens revealed an positive association of ROC1 expression with the SHH pathway activity. Conclusion The current study demonstrated the dysregulation of ROC1-SUFU-GLI2 axis played an important role in bladder cancer progression and targeting of ROC1 expression is warranted further investigation as a novel strategy for future control of bladder cancer.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

ENHANCED SENSITIVITY OF BLADDER CANCER CELLS TO CISPLATIN MEDIATED CYTOTOXICITY AND APOPTOSIS IN VITRO AND IN VIVO BY THE SELECTIVE CYCLOOXYGENASE-2 INHIBITOR JTE-522

2004 ◽  
Vol 172 (4 Part 1) ◽  
pp. 1474-1479 ◽  
Author(s):  
YOICHI MIZUTANI ◽  
HIROYUKI NAKANISHI ◽  
YONG NAN LI ◽  
NODOKA SATO ◽  
AKIHIRO KAWAUCHI ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cyclooxygenase 2 ◽  
Enhanced Sensitivity ◽  
Bladder Cancer Cells
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