The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma

Abstract Background CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.

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Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo

Journal of Neuroscience Research ◽

10.1002/jnr.21690 ◽

2008 ◽

Vol 86 (11) ◽

pp. 2476-2487 ◽

Cited By ~ 16

Author(s):

Kwang-Woo Ahn ◽

Yuyoung Joo ◽

Yoori Choi ◽

Minji Kim ◽

Sang Hyoung Lee ◽

...

Keyword(s):

Cell Cycle ◽

Amyloid Precursor Protein ◽

Precursor Protein ◽

Protein Mutation ◽

Amyloid Precursor Protein Mutation ◽

Related Proteins

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Abstract 2076: Targeting vulnerable aberrant cancer-associated pathways by rationalized triple combination regimens to effectively control urothelial carcinoma cells in vitro and in vivo

10.1158/1538-7445.am2019-2076 ◽

2019 ◽

Author(s):

Hwa-Chain R. Wang ◽

Pawat Pattarawat ◽

Jinquan Wang ◽

Robert Donnell

Keyword(s):

Urothelial Carcinoma ◽

Carcinoma Cells ◽

Triple Combination ◽

Combination Regimens

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Sinomenine, a COX-2 inhibitor, induces cell cycle arrest and inhibits growth of human colon carcinoma cells in vitro and in vivo

Oncology Letters ◽

10.3892/ol.2015.3838 ◽

2015 ◽

Vol 11 (1) ◽

pp. 411-418 ◽

Cited By ~ 17

Author(s):

HAIBO YANG ◽

PEIHAO YIN ◽

ZHAN SHI ◽

YANCHUN MA ◽

CHENGGEN ZHAO ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Human Colon ◽

Carcinoma Cells ◽

Colon Carcinoma Cells ◽

Cycle Arrest ◽

Human Colon Carcinoma ◽

Cox 2

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Luteolin Inhibits Breast Cancer Development and Progression In Vitro and In Vivo by Suppressing Notch Signaling and Regulating MiRNAs

Cellular Physiology and Biochemistry ◽

10.1159/000438535 ◽

2015 ◽

Vol 37 (5) ◽

pp. 1693-1711 ◽

Cited By ~ 42

Author(s):

Da-Wei Sun ◽

He-Da Zhang ◽

Ling Mao ◽

Chang-Fei Mao ◽

Wei Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Notch Signaling ◽

Notch Pathway ◽

Tube Formation ◽

Cancer Development ◽

Notch 1 ◽

Related Proteins

Background/Aims: This study aims to investigate the effect of Luteolin on breast cancer in vitro and in vivo and the interaction between miRNAs and Notch signaling after Luteolin intervention, and illustrates the possible underlying mechanism and regulation loop. Methods: Cell growth/survival assays and cell cycle analyses were performed to evaluate cell survival in vitro. Scratch tests, cell invasion assays and tube formation assays were carried out to analyze cell viability and identify the impact of Luteolin on angiogenesis. Critical components in the Notch pathway including proteins and mRNAs were detected by Western blotting analyses, ELISA assays and real-time reverse transcription-polymerase chain reaction. Matrix metalloproteinases activity was evaluated by gelatin zymography analyses. MiRNAs were analyzed by miRNA expression assays. After MDA-MB-231 cells were separately transfected with Notch-1 siRNA/cDNA and miRNA mimics, the above assays were also carried out to examine potential tumor cell changes. Xenograft models were applied to evaluate the treatment potency of Luteolin in breast cancer. Results: Luteolin significantly inhibited breast cancer cell survival, cell cycle, tube formation and the expression of Notch signaling-related proteins and mRNAs, and regulated miRNAs. After introducing Notch-1 siRNA and miRNA mimics, MDA-MB-231 cells presented with changes in miRNA levels, reduced Notch signaling-related proteins, and decreased tumor survival, invasion and angiogenesis. Conclusion: Luteolin inhibits Notch signaling by regulating miRNAs. However, the effect of miRNAs on the Notch pathway could be either Luteolin-dependent or Luteolin-independent. Furthermore, Notch-1 alteration may inversely change miRNAs levels. Our data demonstrates that Luteolin, miRNAs and the Notch pathway are critical in breast cancer development and prognosis.

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Overexpression of LINC00673 Promotes the Proliferation of Cervical Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.669739 ◽

2021 ◽

Vol 11 ◽

Author(s):

Sheng-Kai Huang ◽

Ruo-Xuan Ni ◽

Wen-Jie Wang ◽

Di Wang ◽

Mei Zhao ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Nude Mice ◽

Siha Cells ◽

Cervical Cancer Cells ◽

Related Proteins

ObjectiveTo study the expression of LINC00673 in cervical cancer and cervical intraepithelial neoplasia (CIN) and to explore the role of LINC00673 in the development of cervical cancer.MethodsThe expression of LINC00673 in serum from cervical cancer patients, CIN patients, and healthy participants was detected by RT-qPCR. The function of LINC00673 in cervical cancer cells was analyzed using in vitro and in vivo experiments.ResultsOur results revealed that serum LINC00673 levels were highest in cervical cancer patients, followed by patients with CIN and healthy controls. In vitro experiments demonstrated that overexpression of LINC00673 enhanced the proliferation and cell cycle progression of HeLa and SiHa cells. In vivo experiments showed that the tumor weight and volume of nude mice subcutaneously injected with LINC00673-overexpressing HeLa cells were larger than those of nude mice injected with control cells (P < 0.05). Western blotting showed that cell cycle-related proteins cyclin A2 and cyclin E and interstitial-associated proteins Snail and N-cadherin were upregulated and p53 signaling pathway-related proteins were downregulated in LINC00673-overexpressing HeLa and SiHa cells.ConclusionLINC00673 plays an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

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Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting

Frontiers in Pharmacology ◽

10.3389/fphar.2021.731386 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lu Li ◽

Huiquan Liu ◽

Weili Tao ◽

Su Wen ◽

Xiaofen Fu ◽

...

Keyword(s):

Colon Cancer ◽

Muscle Atrophy ◽

Muscle Wasting ◽

Expression Level ◽

Soluble Form ◽

C2c12 Myotubes ◽

Hmgb1 Level ◽

Related Proteins

Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present.Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model.Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo.Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.

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Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus

Cellular Physiology and Biochemistry ◽

10.1159/000494008 ◽

2018 ◽

Vol 50 (1) ◽

pp. 317-331 ◽

Cited By ~ 4

Author(s):

Limin Liu ◽

Herui Wang ◽

Jing Cui ◽

Qi Zhang ◽

Wei Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Protein Phosphatase ◽

Mucoepidermoid Carcinoma ◽

Protein Phosphatase 2A ◽

Locally Advanced ◽

Carcinoma Cells ◽

Akt Pathway ◽

Phosphatase 2A

Background/Aims: Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence has indicated that PP2A inhibition exhibits considerable anticancer potency in multiple types of human cancers. However, the efficacy of PP2A inhibition remains unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and metastatic cases with limited systemic treatment. In this study, we demonstrated the therapeutic potency of LB100 in mucoepidermoid carcinoma. Methods: In this study, the expression of PP2A was evaluated using immunohistochemical (IHC) staining. The effects associated with LB100 alone and in combination with cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in vitro, regarding metabolism, proliferation, and migration, and in vivo in a mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and in response to an insulin stimulus, the expression levels and phosphorylation levels of targets in the PI3K-AKT pathway were determined using western blot analysis and immunoblotting. Results: The expression of protein phosphatase 2A was significantly upregulated in the clinical specimens of high-grade MECs compared with those of low-/medium-grade MECs and normal controls. In this article, we report that a small molecule PP2A inhibitor, LB100, decreased cellular viability and glycolytic activity and induced G2/M cell cycle arrest. Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma cells both in vitro and in vivo. PP2A inhibition by LB100 increased the phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues, downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma cells in response to insulin stimulus. Conclusion: These results highlight the translational potential of PP2A inhibition to synergize with cisplatin in mucoepidermoid carcinoma treatment.

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Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder

Diagnostics ◽

10.3390/diagnostics10010054 ◽

2020 ◽

Vol 10 (1) ◽

pp. 54

Author(s):

Yoshitaka Itami ◽

Makito Miyake ◽

Sayuri Ohnishi ◽

Yoshihiro Tatsumi ◽

Daisuke Gotoh ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Migration Ability ◽

Clinical Role ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Carcinoma Of The Bladder ◽

And Migration ◽

Related Proteins

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.

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