Study of LBHD1 Expression with Invasion and Migration of Bladder Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Dong C
PROVIDER: S-EPMC7874779 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The expression status of ZKSCAN3, a zinc-finger transcription factor containing KRAB and SCAN domains, as well as its biological significance, in human bladder cancer remains largely unknown. In the current study, we aimed to determine the functional role of ZKSCAN3 in bladder cancer progression. Immunohistochemistry in tissue specimens detected ZKSCAN3 signals in 138 (93.2%) of 148 urothelial neoplasms, which was significantly higher than in non-neoplastic urothelial tissues [76 (84.4%) of 90; P=0.044]. Correspondingly, the levels of ZKSCAN3 gene were significantly elevated in bladder tumors, compared with those in adjacent normal-appearing bladder mucosae (P=0.008). In a validation set of tissue microarray, significantly higher ZKSCAN3 expression was observed in high-grade and/or muscle-invasive urothelial carcinomas than in low-grade and/or non-muscle-invasive tumors. Two bladder cancer cell lines, UMUC3 and 647V, were found to strongly express ZKSCAN3 protein/mRNA, whereas its expression in 5637 bladder cancer and SVHUC normal urothelium cell lines was very weak. ZKSCAN3 silencing via its short hairpin RNA (shRNA) in UMUC3 and 647V resulted in significant decreases in cell viability/colony formation, cell migration/invasion, and the expression of matrix metalloproteinase (MMP)-2/MMP-9 and oncogenes c-myc/FGFR3, as well as significant increases in apoptosis and the expression of tumor suppressor genes p53/PTEN. ZKSCAN3 overexpression in 5637 also induced cell growth and migration. In addition, ZKSCAN3-shRNA expression considerably retarded tumor formation as well as its subsequent growth in xenograft-bearing mice. These results suggest that ZKSCAN3 plays an important role in bladder cancer outgrowth. Thus, ZKSCAN3 inhibition has the potential of being a therapeutic approach for bladder cancer.
| S-EPMC5288208 | biostudies-literature
Project description:circRNAs have been demonstrated to be key regulators of bladder cancer progression. The present study aimed to investigate the effects of circular RNA (circ)_0067934 in bladder cancer progression. A total of 54 patients with primary bladder cancer were enrolled, and their tumor tissues and adjacent normal bladder tissues were collected. For in vitro functional assays, T24 cells were transfected with sicirc_0067934, and Cell Counting Kit-8 was used to analyze the proliferative capacity of T24 cells. In addition, Transwell and Matrigel assays were used to assess the cell migration and invasion abilities, and a dual-luciferase reporter assay was used to investigate the relationship between miR-1304 and circ_0067934. Finally, reverse transcription-quantitative PCR and western blotting were performed to analyze gene and protein expression levels, respectively. circ_0067934 expression levels were significantly increased in bladder cancer tissues (P<0.001), which was associated with metastasis and a significantly decreased 5-year overall (P<0.05) and disease-free survival (P<0.05). In vitro, T24 cells in the small interfering RNA (si)circ_0067934 group demonstrated significantly reduced proliferation, migration and invasion abilities compared with the si negative control (siNC) group (P<0.01). In addition, the knockdown of circ_0067934 directly increased microRNA (miR)-1304 expression levels in T24 cells. Myc was subsequently discovered to be directly inhibited by miR-1304 and circ_0067934 was observed to increase Myc expression levels in T24 cells through inhibiting miR-1304 expression levels (P<0.01). Compared with the siNC group and sicirc_0067934 + Myc overexpression group, T24 cells in the sicirc_0067934 group exhibited significantly decreased proliferative, migratory and invasive abilities (P<0.01). In conclusion, circ_0067934 was demonstrated to increase bladder cancer cell proliferation, migration and invasion through promoting Myc expression levels via the suppression of miR-1304 expression.
| S-EPMC7185149 | biostudies-literature
Project description:Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer.
| S-EPMC7313018 | biostudies-literature
Project description:Bladder cancer (BC) is the second most common urological tumour in Western countries. Approximately, 80% of patients with BC will present with non-muscle invasive bladder cancer (NMIBC), whereas a quarter will have muscle invasive disease (MIBC) at the time of BC diagnosis. However, patients with NMIBC are at risk of BC recurrence or progression into MIBC, and an MIBC prognosis is determined by the presence of progression and metastasis. Matrix metalloproteinase 2 (MMP2), a type of matrix metalloproteinase (MMP), plays a major role in tumour invasion and is well-characterized in BC prognosis. In BC, the mechanisms regulating MMP2 expression, and, in turn, promote cancer invasion, have hardly been explored. Thrombospondin-4 (THBS4/TSP4) is a matricellular glycoprotein that regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion and extracellular matrix modelling. Based on the results of a meta-analysis in the Gene Expression Profiling Interactive Analysis 2 database, we observed that TSP4 expression levels were consistent with overall survival (OS) rate and BC progression, with the highest expression levels observed in the advanced stages of BC and associated with poor OS rate. In our pilot experiments, incubation with recombinant TSP4 promoted the migration and invasion in BC cells. Furthermore, MMP2 expression levels increased after recombinant TSP4 incubation. TSP4-induced-MMP2 expression and cell motility were regulated via the AKT signalling pathway. Our findings facilitate further investigation into TSP4 silencing-based therapeutic strategies for BC.
| S-EPMC8406484 | biostudies-literature
Project description:Increased expression of CCL18 has been observed in various malignancies and in the urine samples of patients with bladder cancer (BC). However, the roles of CCL18 in the development, progression and metastasis of BC remain unclear. The present study demonstrated that CCL18 expression was significantly associated with advanced clinical stages of BC. Furthermore, exogenous CCL18 promoted cell invasion and migration, and induced cell epithelial?mesenchymal transition (EMT) in BC cells. Western blotting demonstrated that E?cadherin, an epithelial marker, was decreased, whereas matrix metalloproteinase (MMP)?2 and vascular endothelial growth factor (VEGF)?C were increased in CCL18?treated cells. Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in E?cadherin, and increase in MMP?2 and VEGF?C, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18?induced cancer cell invasion, migration and EMT. In conclusion, these data suggested that CCL18 may promote migration, invasion and EMT by binding CCR8 in BC cells. Inhibition of CCL18 activity by blocking CCR8 could be a potential therapeutic strategy for preventing the progression of BC.
| S-EPMC6390063 | biostudies-literature
Project description:The FoxM1 (Forkhead Box M1) transcription factor plays a key role in regulation of cell growth, cell cycle, and transformation. Higher expression of FoxM1 has been observed in various types of human cancers including bladder cancer. However, the exact function of FoxM1 in bladder cancer has not been elucidated. To investigate the cellular and molecular function of FoxM1 in bladder cancer, we measured the consequences of downregulation and upregulation of FoxM1 in bladder cancer cells using MTT assay, wound healing assay, and invasion assay. We found that downregulation of FoxM1 inhibited cell growth, but induced apoptosis in bladder cancer cells. Moreover, we found that inhibition of FoxM1 retarded cell migration and invasion. In line with this, upregulation of FoxM1 led to cell growth promotion and inhibited cell apoptosis in bladder cancer cells. Consistently, upregulation of FoxM1 led to increased cell migration and invasion. Our Western blotting results identified that downregulation of FoxM1 increased p27 level and inhibited VEGF, while overexpression of FoxM1 reduced p27 level and increased VEGF. Our findings suggest that FoxM1 could be a useful target for the treatment of bladder cancer.
| S-EPMC5835828 | biostudies-other
Project description:The role of DNA methyltransferase 3B (DNMT3B) in tumorigenesis and development has been widely recognized; however, the mechanism underlying its action remains unclear. Considering its function in de novo methylation, we aimed to investigate whether DNMT3B plays its role via microRNA (miR)-34a promoter methylation in bladder cancer. We found that DNMT3B expression was low in 10 bladder cancer tissues and high in 20 bladder cancer tissues. miR-34a expression was higher in bladder cancer tissues with low expression of DNMT3B than that in bladder cancer tissues with high expression of DNMT3B. The level of miR-34a was negatively correlated with the level of DNMT3B. The methylation ratio of the miR-34a promoter was positively correlated with the level of DNMT3B and negatively correlated with the level of miR-34a. DNMT3B knockdown increased the expression of miR-34a and the transcriptional activity of the miR-34a promoter, while decreasing miR-34a promoter methylation. DNMT3B knockdown inhibited migration and invasion, while decreasing the protein levels of hepatocyte nuclear factor 4 gamma and Notch1 which are downstream targets of miR-34a. These inhibitory effects of DNMT3B were mitigated by the miR-34a inhibitor. In conclusion, DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer.
| S-EPMC7762500 | biostudies-literature
Project description:BackgroundThis study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism.MethodsFirst, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells.ResultsWound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells.ConclusionERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment.
| S-EPMC6417071 | biostudies-literature
Project description:BackgroundBladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa.MethodsBioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed.ResultsBioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis.ConclusionRAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa.
| S-EPMC7488983 | biostudies-literature
Project description:Ribosome-binding protein 1 (RRBP1) is a marker for colorectal, lung, esophageal and prostate cancer. However, the association between RRBP1 and bladder cancer is not completely understood. The present study aimed to evaluate the expression and function of RRBP1 in bladder cancer. The association between RRBP1 expression and clinicopathological characteristics, as well as the prognosis of bladder cancer was analyzed. RRBP1 expression was further analyzed in bladder cancer cell lines via reverse transcription-quantitative PCR and western blotting. RRBP1 knockdown was established using short hairpin RNAs to investigate the function of RRBP1 in T24 cells. Compared with healthy bladder tissue, RRBP1 expression levels were significantly upregulated in bladder cancer tissue. High RRBP1 expression was associated with tumor stage, lymph node metastasis and shorter overall survival time. RRBP1 protein was highly expressed in bladder cancer cell lines compared with normal SV-HUC-1 cells. Compared with the control group, RRBP1 knockdown inhibited T24 migration and invasion by downregulating the expression of C-C chemokine receptor type 7 (CCR7) protein. In conclusion, the present study indicated that RRBP1 was associated with bladder cancer migration, invasion and prognosis, and CCR7 might serve a role in the process.
| S-EPMC7491031 | biostudies-literature