scholarly journals Superenhancer–transcription factor regulatory network in malignant tumors

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1564-1582
Author(s):  
Yuan Liang ◽  
Linlin Li ◽  
Tian Xin ◽  
Binru Li ◽  
Dalin Zhang
Keyword(s):  
Bladder Cancer ◽  
Malignant Tumor ◽  
Regulatory Network ◽  
Reference Genome ◽  
Malignant Tumors ◽  
Rna Seq ◽  
Human Reference Genome ◽  
Bladder Cancer Cells ◽  
On Chip

Abstract Objective This study aims to identify superenhancer (SE)–transcriptional factor (TF) regulatory network related to eight common malignant tumors based on ChIP-seq data modified by histone H3K27ac in the enhancer region of the SRA database. Methods H3K27ac ChIP-seq data of eight common malignant tumor samples were downloaded from the SRA database and subjected to comparison with the human reference genome hg19. TFs regulated by SEs were screened with HOMER software. Core regulatory circuitry (CRC) in malignant tumor samples was defined through CRCmapper software and validated by RNA-seq data in TCGA. The findings were substantiated in bladder cancer cell experiments. Results Different malignant tumors could be distinguished through the H3K27ac signal. After SE identification in eight common malignant tumor samples, 35 SE-regulated genes were defined as malignant tumor-specific. SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. In vitro experimental data verified the presence of a SE–TF regulatory network in bladder cancer, and SE–TF regulatory network enhanced the malignant phenotype of bladder cancer cells. Conclusion The SE–TF regulatory network with SMAD3 as the core TF may participate in the carcinogenesis of malignant tumors.

scholarly journals DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chin-Hui Lai ◽  
Kexin Xu ◽  
Jianhua Zhou ◽  
Mingrui Wang ◽  
Weiyu Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Tumor Grade ◽  
In Vivo Studies ◽  
Mechanistic Study ◽  
Tumor Promotor ◽  
Bladder Cancer Cells

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.

scholarly journals ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Yuchen Wang ◽  
Jie Wu ◽  
Wenjie Luo ◽  
Hailiang Zhang ◽  
Guohai Shi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Malignant Tumors ◽  
Direct Interaction ◽  
In Vivo Experiments ◽  
Tumor Promotor ◽  
Promising Target ◽  
Bladder Cancer Cells

AbstractBladder cancer is one of the most common malignant tumors in the urinary system. The development and improvement of treatment efficiency require the deepening of the understanding of its molecular mechanism. This study investigated the role of ALPK2, which is rarely studied in malignant tumors, in the development of bladder cancer. Our results showed the upregulation of ALPK2 in bladder cancer, and data mining of TCGA database showed the association between ALPK2 and pathological parameters of patients with bladder cancer. In vitro and in vivo experiments demonstrated that knockdown of ALPK2 could inhibit bladder cancer development through regulating cell proliferation, cell apoptosis, and cell migration. Additionally, DEPDC1A is identified as a potential downstream of ALPK2 with direct interaction, whose overexpression/downregulation can inhibit/promote the malignant behavioral of bladder cancer cells. Moreover, the overexpression of DEPDC1A can rescue the inhibitory effects of ALPK2 knockdown on bladder cancer. In conclusion, ALPK2 exerts a cancer-promoting role in the development of bladder cancer by regulating DEPDC1A, which may become a promising target to improve the treatment strategy of bladder cancer.

scholarly journals Downregulation of MTHFD2 Inhibits the Progression of Bladder Cancer Through PI3K/AKT Signaling Pathways

2022 ◽  
Author(s):  
Xinxi Deng ◽  
Xiaoqiang Liu ◽  
Bing Hu ◽  
Jianyun Liu ◽  
Wensheng Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Tumor Stage ◽  
Akt Signaling ◽  
Rna Seq ◽  
Akt Signaling Pathway ◽  
Low Expression

Abstract Background: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is related to the pathogenesis of many human malignant tumors, but its role in bladder cancer remains poorly understood. We aimed to determine the effect of downregulation of MTHFD2 on the progression of bladder cancer. First, the relationship between MTHFD2 expression and survival time in patients with bladder cancer was analyzed by GEPIA and the UALCAN online database. The expression of MTHFD2 in bladder cancer and adjacent tissues was detected by reverse transcription-quantitative PCR (RT-PCR), Western blot (WB), and tissue microarray. Second, the effects of low expression of MTHFD2 on the proliferation of bladder cancer cell lines were evaluated by CCK-8, Transwell, cell wound scratch, cell cloning, and flow cytometry assays. In vivo, the effect of MTHFD2 silencing on tumorigenicity was determined in nude mice. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway was confirmed by western blotting after RNA sequencing (RNA-seq). Results: The expression of MTHFD2 in bladder cancer tissues was significantly higher and positively correlated with tumor stage and negatively correlated with overall survival. The expression of MTHFD2 in bladder cancer lines was significantly higher and the proliferation, migration, and clone formation ability of bladder cancer cells with low expression of MTHFD2 were significantly decreased in vitro and in vivo. RNA-seq showed that the differential genes were enriched in the PI3K/Akt signaling pathway. WB revealed that the expression of PI3K/AKT protein was downregulated. Conclusions: Our findings indicated that downregulation of MTHFD2 can reduce the progression of bladder cancer through inhibited PI3K-AKT signal pathway and may be provided a new approach for the diagnosis and treatment of bladder cancer.

SYSTEMATIC IN VITRO EVALUATION OF SURVIVIN DIRECTED ANTISENSE OLIGODEOXYNUCLEOTIDES IN BLADDER CANCER CELLS

2004 ◽  
Vol 171 (6 Part 1) ◽  
pp. 2471-2476 ◽  
Author(s):  
SUSANNE FUESSEL ◽  
BERND KUEPPERS ◽  
SHUANGLI NING ◽  
MATTHIAS KOTZSCH ◽  
KAI KRAEMER ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Antisense Oligodeoxynucleotides ◽  
In Vitro Evaluation ◽  
Bladder Cancer Cells

scholarly journals lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

2021 ◽  
Vol 22 (3) ◽  
pp. 1407
Author(s):  
Hongxia Liu ◽  
Wang Zheng ◽  
Qianping Chen ◽  
Yuchuan Zhou ◽  
Yan Pan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Rna Seq ◽  
Cellular Autophagy ◽  
First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

scholarly journals Peptide-guided JC polyomavirus-like particles specifically target bladder cancer cells for gene therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Hong Lai ◽  
Chiung-Yao Fang ◽  
Ming-Chieh Chou ◽  
Mien-Chun Lin ◽  
Cheng-Huang Shen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Suicide Gene ◽  
Transduction Efficiency ◽  
Ligand Molecule ◽  
Jc Polyomavirus ◽  
Exogenous Dna ◽  
Bladder Cancer Cells

AbstractThe ultimate goal of gene delivery vectors is to establish specific and effective treatments for human diseases. We previously demonstrated that human JC polyomavirus (JCPyV) virus-like particles (VLPs) can package and deliver exogenous DNA into susceptible cells for gene expression. For tissue-specific targeting in this study, JCPyV VLPs were conjugated with a specific peptide for bladder cancer (SPB) that specifically binds to bladder cancer cells. The suicide gene thymidine kinase was packaged and delivered by SPB-conjugated VLPs (VLP-SPBs). Expression of the suicide gene was detected only in human bladder cancer cells and not in lung cancer or neuroblastoma cells susceptible to JCPyV VLP infection in vitro and in vivo, demonstrating the target specificity of VLP-SPBs. The gene transduction efficiency of VLP-SPBs was approximately 100 times greater than that of VLPs without the conjugated peptide. JCPyV VLPs can be specifically guided to target particular cell types when tagged with a ligand molecule that binds to a cell surface marker, thereby improving gene therapy.

scholarly journals Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder Cancer Cells In Vitro

2021 ◽  
pp. 1-17
Author(s):  
Laura E. Griffin ◽  
Sarah E. Kohrt ◽  
Atul Rathore ◽  
Colin D. Kay ◽  
Magdalena M. Grabowska ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Microbial Metabolites ◽  
Bladder Cancer Cells

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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