scholarly journals Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ke-Hung Tsui ◽  
Shyi-Wu Wang ◽  
Li-Chuan Chung ◽  
Tsui-Hsia Feng ◽  
Tzu-Yi Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Carcinoma ◽  
Interleukin 6 ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Human Bladder ◽  
T24 Cells ◽  
Bladder Carcinoma Cells

Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cellsin vitroandin vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasionin vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN), N-myc downstream gene 1 (NDRG1), and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

scholarly journals Transgelin, a p53 and PTEN-Upregulated Gene, Inhibits the Cell Proliferation and Invasion of Human Bladder Carcinoma Cells in Vitro and in Vivo

2019 ◽  
Vol 20 (19) ◽  
pp. 4946 ◽  
Author(s):  
Tsui ◽  
Lin ◽  
Chang ◽  
Hou ◽  
Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Bladder Carcinoma ◽  
Carcinoma Cells ◽  
Human Bladder ◽  
Ectopic Overexpression ◽  
Proliferation And Invasion ◽  
Bladder Carcinoma Cells

Transgelin (TAGLN/SM22-α) is a regulator of the actin cytoskeleton, affecting the survival, migration, and apoptosis of various cancer cells divergently; however, the roles of TAGLN in bladder carcinoma cells remain inconclusive. We compared expressions of TAGLN in human bladder carcinoma cells to the normal human bladder tissues to determine the potential biological functions and regulatory mechanisms of TAGLN in bladder carcinoma cells. Results of RT-qPCR and immunoblot assays indicated that TAGLN expressions were higher in bladder smooth muscle cells, fibroblast cells, and normal epithelial cells than in carcinoma cells (RT-4, HT1376, TSGH-8301, and T24) in vitro. Besides, the results of RT-qPCR revealed that TAGLN expressions were higher in normal tissues than the paired tumor tissues. In vitro, TAGLN knockdown enhanced cell proliferation and invasion, while overexpression of TAGLN had the inverse effects in bladder carcinoma cells. Meanwhile, ectopic overexpression of TAGLN attenuated tumorigenesis in vivo. Immunofluorescence and immunoblot assays showed that TAGLN was predominantly in the cytosol and colocalized with F-actin. Ectopic overexpression of either p53 or PTEN induced TAGLN expression, while p53 knockdown downregulated TAGLN expression in bladder carcinoma cells. Our results indicate that TAGLN is a p53 and PTEN-upregulated gene, expressing higher levels in normal bladder epithelial cells than carcinoma cells. Further, TAGLN inhibited cell proliferation and invasion in vitro and blocked tumorigenesis in vivo. Collectively, it can be concluded that TAGLN is an antitumor gene in the human bladder.

scholarly journals Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 980 ◽  
Author(s):  
Ke-Hung Tsui ◽  
Chen-Pang Hou ◽  
Kang-Shuo Chang ◽  
Yu-Hsiang Lin ◽  
Tsui-Hsia Feng ◽  
...  
Keyword(s):  
Bladder Carcinoma ◽  
Annexin V ◽  
Carcinoma Cells ◽  
Gene Expressions ◽  
T24 Cells ◽  
Apoptosis Assay ◽  
Induced Apoptosis ◽  
Bladder Carcinoma Cells

Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS2O3) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.

scholarly journals Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 10 ◽  
Author(s):  
Yu-Hsiang Lin ◽  
Ke-Hung Tsui ◽  
Kang-Shuo Chang ◽  
Chen-Pang Hou ◽  
Tsui-Hsia Feng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Suppressor ◽  
Bladder Carcinoma ◽  
Suppressor Gene ◽  
Carcinoma Cells ◽  
Human Bladder ◽  
Maspin Expression ◽  
Bladder Carcinoma Cells

Maspin is a member of the clade B serine protease inhibitor superfamily and exhibits diverse regulatory effects in various types of solid tumors. We compared the expressions of maspin and determined its potential biological functions and regulatory mechanisms in bladder carcinoma cells in vitro and in vivo. The results of RT-qPCR indicated that maspin expressed significantly lower levels in the bladder cancer tissues than in the paired normal tissues. The immunohistochemical assays of human bladder tissue arrays revealed similar results. Maspin-knockdown enhanced cell invasion whereas the overexpression of maspin resulted in the opposite process taking place. Knockdown of maspin also enhanced tumorigenesis in vivo and downregulated protein levels of acetyl-histone H3. Moreover, in bladder carcinoma cells, maspin modulated HDAC1 target genes, including cyclin D1, p21, MMP9, and vimentin. Treatment with MK2206, which is an Akt inhibitor, upregulated maspin expression, whereas PTEN-knockdown or PTEN activity inhibitor (VO-OHpic) treatments demonstrated reverse results. The ectopic overexpression of p53 or camptothecin treatment induced maspin expression. Our study indicated that maspin is a PTEN-upregulated and p53-upregulated gene that blocks cell growth in vitro and in vivo, and may act as an HDAC1 inhibitor in bladder carcinoma cells. We consider that maspin is a potential tumor suppressor gene in bladder cancer.

scholarly journals MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769167 ◽  
Author(s):  
Ju Guo ◽  
Runfu Cao ◽  
Xingwei Yu ◽  
Zewen Xiao ◽  
Zhiwen Chen
Keyword(s):  
Nuclear Receptor ◽  
Bladder Carcinoma ◽  
Messenger Rna ◽  
Tumor Tissue ◽  
Protein Translation ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Nuclear Receptor Coactivator ◽  
Bladder Carcinoma Cells

The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3′-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.

scholarly journals Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1486 ◽  
Author(s):  
Chang ◽  
Tsui ◽  
Lin ◽  
Hou ◽  
Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Prostate Carcinoma ◽  
Immunohistochemical Analysis ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Akt Inhibitor ◽  
Gene Expressions

: Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.

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