scholarly journals Effects of the Zinc Finger Protein 485 (ZNF485) on the Proliferation, Metastasis and Invasion of Bladder Cancer Cells

2021 ◽  
pp. 1-8
Author(s):  
Dabing Huang ◽  
Yiao Tan ◽  
Fangfang Zhao ◽  
Chunbao Zang ◽  
Shuhan Liu ◽  
...  

Objectives: Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. The limited progress on the diagnostics and treatment largely impedes the survival of bladder cancer patients. Methods: Potential therapeutic biomarkers are urgently needed for future clinic treatment. We performed the RNA-seq assays and identified a new gene zinc finger protein 485, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients. Results: We found that inhibition of ZNF485 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation and promotes the apoptosis of cancer cells. Furthermore, the wound healing and invasion assays showed that down-regulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-siRNA transfected obviously inhibited tumor growth in nude mice. Conclusion: Taken together, the results provide evidence that ZNF485 is involved in the tumorigenesis of bladder cancer, which might be a potential therapeutic biomarker for the treatment of this disease.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 333-333
Author(s):  
Qiang Li ◽  
Andrew Bell ◽  
Emmet Jordan ◽  
Sizhi Paul Gao ◽  
Jennifer Ma ◽  
...  

333 Background: Genetic alterations within ERCC2 correlate with extraordinary responses to neoadjuvant cisplatin-based chemotherapy and bladder-sparing ionizing radiation (IR) in muscle-invasive bladder cancer (MIBC). Two studies correlated ERCC2 mutations with pathologic response to chemotherapy and improved disease-free and bladder intact survival following trimodality therapy. We sought to characterize the biological significance of these mutations in bladder cancer cells using CRISPR/Cas9-mediated ablation of ERCC2 function. Methods: The ERCC2 T484A/M point mutation was the most common alteration (4 of 36 patients) within a prospectively collected cohort of 299 bladder cancer patients sequenced at our institution. We infected the ERCC2 wild-type KU19-19 bladder cancer cell line with a CRISPR/Cas9 lentivirus targeting residues 481-487 of ERCC2 and identified a cell clone harboring an ERCC2 in-frame deletion (M483_T484del). Following exposure to cisplatin and IR, cell viability was examined using Cell-titer Glo and clonogenic assays. Apoptosis was gauged by subG1 cell fraction measurement by flow cytometry. Results: ERCC2 mutant cells exhibited significantly increased cisplatin sensitivity compared to parental cells (IC50 0.3uM vs 2.0uM, p < 0.0001). Cisplatin treatment after 48 hours resulted in increased apoptosis in ERCC2 mutant vs parental cells (sub-G1 fraction 52% vs 16%, p = 0.01). ERCC2 mutant cells were more sensitive to combined IR (2 Gy) and cisplatin (1uM) compared to parental cells (SF2Gy (surviving fraction) 17 % vs 60%). Conclusions: ERCC2 mutations enhance cisplatin and IR sensitivity in a bladder cancer cell line model. ERCC2 alterations are likely the genetic basis for extraordinary response to cisplatin chemotherapy and IR in MIBC patients. Prospective genetic sequencing may help select ERCC2 mutant MIBC patients who are most likely to respond to chemotherapy or trimodality bladder-sparing therapy.


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1607
Author(s):  
Ana T. P. C. Gomes ◽  
Rosa Fernandes ◽  
Carlos F. Ribeiro ◽  
João P. C. Tomé ◽  
Maria G. P. M. S. Neves ◽  
...  

Novel triazole-porphyrin derivatives (TZ-PORs) were synthesized through the Heck reaction and then incorporated into polyvinylpyrrolidone (PVP) micelles. After verifying that this incorporation did not compromise the photophysical and chemical features of TZ-PORs as photosensitizers, the phototoxicity of the formulations towards cancer cells was screened. Biological studies show high photodynamic activity of all PVP-TZ-POR formulations against a bladder cancer cell line with a particular highlight to PVP-TZ-POR 7e and 7f that are able to significantly reduce HT-1376 cell viability, while they had no effect on control ARPE-19 cells.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiawa Mao ◽  
Nanzhang ◽  
Jiaquao Xiao ◽  
Huifeng Wu ◽  
Kefeng Ding

Purpose. To investigate the effect of hypoxia on chemoresistance and the underlying mechanism in bladder cancer cells. Methods. BIU-87 bladder cancer cell line was treated with cisplatin under hypoxic and normoxic conditions and tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting. All the data were expressed as mean ± standard   error from three independent experiments and analyzed by multiple t -tests. Results. Apoptosis of bladder cancer cells caused by cisplatin was attenuated in hypoxic conditions. Hypoxia enhanced autophagy caused by cisplatin. The autophagy inhibitor and HIF-1α inhibitor can reverse the chemoresistance in hypoxic condition. Apoptosis and autophagy of bladder cancer cells were downregulated by HIF-1α inhibitor YC-1. Hypoxia-induced autophagy enhanced chemoresistance to cisplatin via the HIF-1 signaling pathway. Conclusion. Resistance to cisplatin in BIU-87 bladder cancer cells under hypoxic conditions can be explained by activation of autophagy, which is regulated by HIF-1α-associated signaling pathways. The hypoxia–autophagy pathway may be a target for improving the efficacy of cisplatin chemotherapy in bladder cancer.


2013 ◽  
Vol 108 (4) ◽  
pp. 973-982 ◽  
Author(s):  
N Wagener ◽  
J Bulkescher ◽  
S Macher-Goeppinger ◽  
I Karapanagiotou-Schenkel ◽  
G Hatiboglu ◽  
...  

2021 ◽  
Vol 67 (3) ◽  
pp. 278-288
Author(s):  
N.S. Ionov ◽  
M.A. Baryshnikova ◽  
E.V. Bocharov ◽  
P.V. Pogodin ◽  
A.A. Lagunin ◽  
...  

Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: — the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.


10.1038/71717 ◽  
2000 ◽  
Vol 24 (1) ◽  
pp. 71-74 ◽  
Author(s):  
Parastoo Momeni ◽  
Gernot Glöckner ◽  
Olaf Schmidt ◽  
Diane von Holtum ◽  
Beate Albrecht ◽  
...  

2014 ◽  
Vol 460 (1) ◽  
pp. 69-80 ◽  
Author(s):  
Yi-Chien Lu ◽  
Chiung-Nien Chen ◽  
Chia-Ying Chu ◽  
JenHer Lu ◽  
Bo-Jeng Wang ◽  
...  

We demonstrated that calreticulin regulated bladder cancer cell adhesion through modifying α1,2-linked glycan on β1-integrin, which was catalysed by fucosyltransferase 1. Most importantly, higher levels of fucosylation directly activated β1-integrin. We provide a potential clinical treatment strategy for bladder cancer patients.


2010 ◽  
Vol 293 (6) ◽  
pp. 1002-1009 ◽  
Author(s):  
Gui-Ling Wang ◽  
Chun-Yu Wang ◽  
Xin-Ze Cai ◽  
Wei Chen ◽  
Xiao-Hui Wang ◽  
...  

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