Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

ABSTRACT: The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.

SUBMITTER: Lin LF

PROVIDER: S-EPMC3237114 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

Lin Li-Fang LF Chuang Chih-Hung CH Li Chien-Feng CF Liao Ching-Chun CC Cheng Chun-Pei CP Cheng Tian-Lu TL Shen Meng-Ru MR Tseng Joseph T JT Chang Wen-Chang WC Lee Wen-Hwa WH Wang Ju-Ming JM

Cancer research 20091208 1

The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of ...[more]

PMID: 19996286

Similar Datasets

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation.

Project description:Phosphorylation is a recently established cause of phosphatase and tensin homolog (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In pancreatic cancer, this phenomenon has not been reported. Based on database and clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of PTEN, was significantly down-regulated in pancreatic cancer as compared to adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the proliferation and migration abilities of pancreatic cancer cells and led to significantly decreased PTEN phosphorylation and AKT phosphorylation by interacting with wild-type PTEN. In addition, a transcription factor-activation assay supported that PDZK1 overexpression enhanced the anti-oncogene function of PTEN by regulating the activities of its downstream transcription factors, including p53, NF-?B, and FOXO1. In vivo, nude mice stably over-expressing PDZK1 had lower tumour weights and volumes and showed significantly down-regulated PTEN phosphorylation in xenograft tumour tissues as compared to the control group. Moreover, low PDZK1 expression strongly correlated with advanced stage and poor prognosis of patients with pancreatic ductal adenocarcinoma. In conclusion, our study elucidated the tumour-suppressor role of PDZK1 in pancreatic cancer through down-regulating PTEN phosphorylation, and established PDZK1 as a potential novel prognostic marker for pancreatic cancer.

| S-EPMC5641177 | biostudies-other

miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism.

Project description:Dysregulation of miRNA expression is associated with multiple diseases, including cancers, in which small RNAs can have either oncogenic or tumor suppressive functions. Here we investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. RNA-seq analysis of the ovarian cancer cell line A2780 revealed that overexpression of miR-450a suppressed multiple genes involved in the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-450a reduced tumor migration and invasion and increased anoikis in A2780 and SKOV-3 cell lines and reduced tumor growth in an ovarian tumor xenographic model. Combined AGO-PAR-CLIP and RNA-seq analysis identified a panel of potential miR-450a targets, of which many, including TIMMDC1, MT-ND2, ACO2, and ATP5B, regulate energetic metabolism. Following glutamine withdrawal, miR-450a overexpression decreased mitochondrial membrane potential but increased glucose uptake and viability, characteristics of less invasive ovarian cancer cell lines. In summary, we propose that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which leads to decreased production of lipids, amino acids, and nucleic acids, as well as inhibition of signaling pathways associated with EMT. SIGNIFICANCE: miR-450a limits the metastatic potential of ovarian cancer cells by targeting a set of mitochondrial mRNAs to reduce glycolysis and glutaminolysis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/13/3294/F1.large.jpg.

| S-EPMC6606360 | biostudies-literature

CircSPIDR acts as a tumour suppressor in cervical adenocarcinoma by sponging miR-431-5p and regulating SORCS1 and CUBN expression.

Project description:To identify circular RNAs (circRNAs) with tumor suppressor activity against cervical adenocarcinoma, we compared the circRNA levels of cervical adenocarcinoma and normal cervical tissues. We found that circSPIDR was dramatically downregulated in cervical adenocarcinoma tissues. In cervical adenocarcinoma cells, overexpression of circSPIDR reduced cell viability, inhibited colony formation and promoted apoptosis, whereas knockdown of circSPIDR exerted the opposite effects. CircSPIDR overexpression also suppressed the tumorigenicity of cervical adenocarcinoma cells in a xenograft mouse model. CircSPIDR was found to sponge miR-431-5p, thereby de-repressing sortin-related VPS10 domain-containing receptor 1 (SORCS1) and cubilin (CUBN) and inhibiting the development of cervical adenocarcinoma. In clinical cervical samples, circSPIDR expression correlated negatively with miR-431-5p expression and positively with SORCS1 and CUBN expression. These results demonstrated that circSPIDR suppresses cervical adenocarcinoma by competitively binding to miR-431-5p, thus upregulating SORCS1 and CUBN. These findings suggest circSPIDR could serve as a novel therapeutic target for treatment of cervical adenocarcinoma patients.

| S-EPMC8351706 | biostudies-literature

LINC00703 Acts as a Tumor Suppressor via Regulating miR-181a/KLF6 Axis in Gastric Cancer.

Project description:Purpose:Long noncoding RNA 00703 (LINC00703) was found originating from a region downstream of Kruppel-like factor 6 (KLF6) gene, having 2 binding sites for miR-181a. Since KLF6 has been reported as a target of miR-181a in gastric cancer (GC), this study aims to investigate whether LINC00703 regulates the miR-181a/KLF6 axis and plays a functional role in GC pathogenesis. Materials and Methods:GC tissues, cell lines, and nude mice were included in this study. RNA binding protein immunoprecipitation (RIP) and pull-down assays were used to evaluate interaction between LINC00703 and miR-181a. Quantitative real-time polymerase chain reaction and western blot were applied for analysis of gene expression at the transcriptional and protein levels. A nude xenograft mouse model was used to determine LINC00703 function in vivo. Results:We revealed that LINC00703 competitively interacts with miR-181a to regulate KLF6. Overexpression of LINC00703 inhibited cell proliferation, migration/invasion, but promoted apoptosis in vitro, and arrested tumor growth in vivo. LINC00703 expression was found to be decreased in GC tissues, which was positively correlated with KLF6, but negatively with the miR-181a levels. Conclusions:LINC00703 may have an anti-cancer function via modulation of the miR-181a/KLF6 axis. This study also provides a new potential diagnostic marker and therapeutic target for GC treatment.

| S-EPMC6928083 | biostudies-literature

CDC37L1 acts as a suppressor of migration and proliferation in gastric cancer by down-regulating CDK6.

Project description:The co-chaperone protein CDC37 (Cell division cycle 37) is well known to regulate multiple protein kinases and involved in tumor progression. However to date, little is known about its analogue CDC37L1 (Cell division cycle 37 like 1) in tumorigenesis. This study aimed to explore the expression and function of CDC37L1 in gastric cancer (GC). The immunohistochemical staining in a tissue microarray showed a weak expression of CDC37L1 in high grade GC tissues compared with low grade tissues. Consistently, data from online database analysis demonstrated that CDC37L1 level was decreased in stage 4 patients and low expression of CDC37L1 indicated a poor prognosis. Functional studies revealed that CDC37L1 could inhibit GC cell proliferation and migration in CCK8, EdU incorporation, colony formation and transwell assays. In the meantime, CDC37L1 also inhibited the tumorigenicity of GC cells in nude mice. Mechanistically, we found that CDC37L1 had an impact on CDK6 protein expression by western blotting. Palbociclib, a specific CDK4/6 inhibitor, was discovered to block the rapid growth phenotype of GC cells induced by CDC37L1 silencing. Taken together, these findings unveiled a tumor-suppressive role of CDC37L1 in GC, and CDK6 may act as a downstream effector in this process.

| S-EPMC8100790 | biostudies-literature

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.

Project description:BackgroundThe current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer.MethodsThe regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1.ResultsBioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression.ConclusionOur study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.

| S-EPMC10866439 | biostudies-literature

MicroRNA-135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer.

Project description:The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR-135a-5p expression is often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA-135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR-135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a-VLDLR downstream signaling. Together, these results suggested that the miR-135a-VLDLR-p38 axis may contribute to GBC cell proliferation.

| S-EPMC4317855 | biostudies-literature

MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy.

Project description:Metastasis, the main cause of cancer-related death, has traditionally been viewed as a late-occurring process during cancer progression. Using the MMTV-PyMT luminal B breast cancer model, we demonstrate that the lung metastatic niche is established early during tumorigenesis. We found that matrix metalloproteinase 9 (MMP9) is an important component of the metastatic niche early in tumorigenesis and promotes circulating tumor cells to colonize the lungs. Blocking active MMP9, using a monoclonal antibody specific to the active form of gelatinases, inhibited endogenous and experimental lung metastases in the MMTV-PyMT model. Mechanistically, inhibiting MMP9 attenuated migration, invasion, and colony formation and promoted CD8+ T cell infiltration and activation. Interestingly, primary tumor burden was unaffected, suggesting that inhibiting active MMP9 is primarily effective during the early metastatic cascade. These findings suggest that the early metastatic circuit can be disrupted by inhibiting active MMP9 and warrant further studies of MMP9-targeted anti-metastatic breast cancer therapy.

| S-EPMC6856766 | biostudies-literature

Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma.

Project description:Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma.

| S-EPMC5400533 | biostudies-literature

MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells.

Project description:Chondrosarcomas and osteosarcomas are malignant bone tumors with a poor prognosis when unresectable or metastasized. Moreover, radiotherapy and chemotherapy could be ineffective. MiRNAs represent an alternative therapeutic approach. Based on high-throughput functional screening, we identified four miRNAs with a potential antiproliferative effect on SW1353 chondrosarcoma cells. Individual functional validations were then performed in SW1353 cells, as well as in three osteosarcoma cell lines. The antiproliferative and cytotoxic effects of miRNAs were evaluated in comparison with a positive control, miR-342-5p. The cytotoxic effect of four selected miRNAs was not confirmed on SW1353 cells, but we unambiguously revealed that miR-4270 had a potent cytotoxic effect on HOS and MG-63 osteosarcoma cell lines, but not on SaOS-2 cell line. Furthermore, like miR-342-5p, miR-4270 induced apoptosis in these two cell lines. In addition, we provided the first report of Bcl-xL as a direct target of miR-4270. MiR-4270 also decreased the expression of the anti-apoptotic protein Mcl-1, and increased the expression of the pro-apoptotic protein Bak. Our findings demonstrated that miR-4270 has tumor suppressive activity in osteosarcoma cells, particularly through Bcl-xL downregulation.

| S-EPMC10501397 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data