scholarly journals Wilms’ Tumor 1-Associating Protein Promotes Prostate Cancer Proliferation via Upregulation of CDK4 Transcript

2020 ◽  
Author(s):  
Lei Zhang ◽  
Yiren Gao ◽  
Jun Wang ◽  
Linghui Liang ◽  
Yifei Cheng ◽  
...  

Abstract Background: Wilms’ tumor 1-associating protein (WTAP) plays an important role in cell physiological function and have attracted increased interest in cancer research recently. Cyclin-dependent protein kinases (CDKs) are known to participate in regulating the cell cycle and often connected to many malignancies in tumor. We aim to explore whether WTAP or CDKs could play an role in the initiation and progression of prostate cancer(PCa) and hope to provide new insights into PCa treatment and prognostic. Methods: Quantitative real-time PCR, western blotting and immunohistochemistry were performed to explore the expression of WTAP and CDK4 in prostate cancer tissues and cell lines. The survival analysis was used to investigate the association between WTAP expression and the clinical outcomes of prostate cancer. Prostate cancer cell lines were stably transfected with lentivirus approach. CCK-8 assay, colony formation assay, cell invasion and migration assay, cell cycle assay and tumorigenesis in nude mice were performed to study the effect of WTAP in prostate cancer cell lines. RNA immunoprecipitation assay, dual-luciferase reporter assay and siRNA transfection were performed to verify the direct binding sites of WTAP with CDK4 transcript.Results: In prostate cancer tissues and cell lines, WTAP was significantly up-regulated and high expression of WTAP was connected to poor clinical outcomes. Additionally, cell function test indicated that overexpression of WTAP in prostate cancer cell lines could promote cell proliferation, while knocking down showed an opposite results. Subcutaneous xenograft tumor model revealed that overexpression of WTAP could induce tumorigenesis in vivo. Mechanism study showed that CDK4 expression could regulate the expression level of WTAP. Moreover, WTAP could directly bind to 3’-UTR of CDK4 transcript and enhance its stability. Furthermore, specific inhibitors of CDK4 as well as small interfering RNA (siRNA) of CDK4 reversed the promotion of proliferation induced by WTAP.Conclusions: These data indicated that WTAP may act as an oncogenic in prostate cancer by directly binding to CDK4 3’-UTR and stabilizing its transcript which might provide new insights into prostate cancer treatment and prognostic.

2020 ◽  
Author(s):  
Lei Zhang ◽  
Yiren Gao ◽  
Jun Wang ◽  
Linghui Liang ◽  
Yifei Cheng ◽  
...  

Abstract Background: Wilms’ tumor 1-associating protein (WTAP) plays an important role in cell physiological function and have attracted increased interest in cancer research recently. Cyclin-dependent protein kinases (CDKs) are known to participate in regulating the cell cycle and often connected to many malignancies in tumor. We aim to explore whether WTAP or CDKs could play an role in the initiation and progression of prostate cancer(PCa) and hope to provide new insights into PCa treatment and prognostic. Methods: Quantitative real-time PCR, western blotting and immunohistochemistry were performed to explore the expression of WTAP and CDK4 in prostate cancer tissues and cell lines. The survival analysis was used to investigate the association between WTAP expression and the clinical outcomes of prostate cancer. Prostate cancer cell lines were stably transfected with lentivirus approach. CCK-8 assay, colony formation assay, cell invasion and migration assay, cell cycle assay and tumorigenesis in nude mice were performed to study the effect of WTAP in prostate cancer cell lines. RNA immunoprecipitation assay, dual-luciferase reporter assay and siRNA transfection were performed to verify the direct binding sites of WTAP with CDK4 transcript.Results: In prostate cancer tissues and cell lines, WTAP was significantly up-regulated and high expression of WTAP was connected to poor clinical outcomes. Additionally, cell function test indicated that overexpression of WTAP in prostate cancer cell lines could promote cell proliferation, while knocking down showed an opposite results. Subcutaneous xenograft tumor model revealed that overexpression of WTAP could induce tumorigenesis in vivo. Mechanism study showed that CDK4 expression could regulate the expression level of WTAP. Moreover, WTAP could directly bind to 3’-UTR of CDK4 transcript and enhance its stability. Furthermore, specific inhibitors of CDK4 as well as small interfering RNA (siRNA) of CDK4 reversed the promotion of proliferation induced by WTAP.Conclusions: These data indicated that WTAP may act as an oncogenic in prostate cancer by directly binding to CDK4 3’-UTR and stabilizing its transcript which might provide new insights into prostate cancer treatment and prognostic.


2015 ◽  
Vol 11 (1) ◽  
pp. 130
Author(s):  
Nai-Xiong Peng ◽  
Chun-Xiao Liu ◽  
Xi-Sheng Wang ◽  
Ze-Jian Zhang ◽  
Su-Cai Liao

<p class="Abstract">Prostate cancer is major cause of cancer related deaths worldwide in men. There are new treatment methods and drugs are being developed with promising results in two of the prostate cancer cell lines (PPC-1 and TSU-Pr1). These two cells were treated with 20 uM of axitinib combined with dasatinib for 6-72 hours. The cell viability assessed by the cytotoxicity assay. Various regulatory genes such as c-KIT, cell cycle and apoptosis and angiogenic factors were also studied. The enzyme activity of apoptosis efector caspase-3 was colorimetrically determined. Axitinib and dasatinib combination lowered the survival rate of PPC-1 cells but enhanced the survival rate of TSU-Pr1 cells. The protein expression levels in apoptosis and angiogenesis factors were also found to be in contrast between the two cell lines. PPC-1 and TSU-Pr1 cells displayed a different response to axitinib with dasatinib, which explains different expression levels of regulators of cell-cycle, apoptosis and angiogenesis.</p><p> </p>


The Prostate ◽  
2011 ◽  
Vol 72 (4) ◽  
pp. 361-375 ◽  
Author(s):  
Mahmoud Aghaei ◽  
Fatemeh Karami-Tehrani ◽  
Mojtaba Panjehpour ◽  
Siamak Salami ◽  
Faranak Fallahian

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Rodrigo Ramos ◽  
María Elena Hernández ◽  
Ivette Bravo ◽  
Rafael Ramos ◽  
Cynthia Fernández ◽  
...  

2020 ◽  
Vol 21 (22) ◽  
pp. 8724
Author(s):  
Jochen Rutz ◽  
Sarah Thaler ◽  
Sebastian Maxeiner ◽  
Felix K.-H. Chun ◽  
Roman A. Blaheta

Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1–20 µM) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Simon Mahoney ◽  
Frank Arfuso ◽  
Michael Millward ◽  
Arun Dharmarajan

Foods ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 201 ◽  
Author(s):  
Nathalia da Costa Pereira Soares ◽  
Monique de Barros Elias ◽  
Clara Lima Machado ◽  
Bruno Boquimpani Trindade ◽  
Radovan Borojevic ◽  
...  

Lycopene is more bioavailable in processed tomato products than in raw tomatoes, since arrangement of cis-isomers of lycopene during food processing and storage may increase its biological activity. The aim of the study is evaluate the influence of lycopene content from different tomato-based food products (extract, paste, ketchup and sauce) on cell proliferation, cell cycle, and rate of apoptosis of human prostate cancer cell lines. DU-145 and PC-3 cell lines were treated with lycopene content from different tomato-based food products (500–5000 μg/mL) for 96 h. The data showed a decrease in cell viability in both DU-145 and PC-3 cells after treatment with all lycopene extracts from tomato-based food products. Analysis of cell cycle revealed a decrease in the percentage of prostate cancer cells in G0/G1 and G2/M phases after 96 h of treatment when using lycopene content from tomato paste and tomato extract. However, lycopene extracted from tomato sauce and ketchup promoted a decrease in the percentage of cells in G0/G1 phase and an increase in S and G2/M phases after 96 h of treatment. Lycopene content from all of those tomato-based food products also increased apoptosis in both prostate cancer cell lines. In this regard, lycopene has proved to be a potent inhibitor of cell viability, arrest cell cycle and increase the apoptosis in human prostate cancer cells, suggesting an effect in the balance of human prostate cancer cell lines growth.


2021 ◽  
Vol 43 (3) ◽  
pp. 1518-1528
Author(s):  
Youssef Saeed Alghamdi ◽  
Osama Moseilhy Saleh ◽  
Nada Alqadri ◽  
Mutaib Mosaued Mashraqi ◽  
Omar Bahattab ◽  
...  

The goal of this study was to investigate whether Ducrosia flabellifolia and Savignya parviflora methanol extract the have effect on colon and prostate cancer cell lines. Analysis of total content of phenolics and flavonoids of each plant extract was carried out. Cytotoxic effect, cell cycle analysis, induction of apoptosis and gene expression of Bcl-2 and Bax genes were studied. Obtained results indicated that, the plant extracts exhibit growth inhibition of used cancer cell lines and induced apoptosis as well as arresting of cell cycle. At the molecular level, changes in gene expression were detected via qPCR and confirmed by western blotting. The exhibited anticancer potentialities of plant extracts against utilized cancer cell lines are due to its containing bioactive compounds. Further detailed isolation, fractionation and characterization of bioactive compounds are needed.


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