Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF-κB signaling pathway in colorectal cancer cells.

ABSTRACT: GNA13 has been found overexpressed in various types of cancer, which is related to tumor metastasis and progression. However, the biological functions of GNA13 in colorectal cancer (CRC) progression remain unclear. This study aimed to explore the role of GNA13 in CRC and investigate the mechanism of how GNA13 promotes tumor growth. Interestingly, our findings showed that GNA13 is commonly upregulated in CRC, where these events are associated with a worse histologic grade and poor survival. Increased expression levels of GNA13 promoted cell growth, migration, invasion, and epithelial-mesenchymal transition, whereas GNA13 silencing abrogated these malignant phenotypes. In addition, overexpressing GNA13 in cancer cells increased the levels of the chemokines CXCL1, CXCL2, and CXCL4, which contributed to CRC proliferation and colony formation. Moreover, our mechanistic investigations suggest that the NF-κB/p65 signaling pathway was activated by the increase in GNA13 levels. Inhibiting the NF-κB/p65 pathway with an inhibitor decreased GNA13-induced migration, invasion and CXCL chemokine level increases, indicating the critical role of NF-κB/p65 signaling in mediating the effects of GNA13 in CRC. Together, these results demonstrate a key role of GNA13 overexpression in CRC that contributes to malignant behavior in cancer cells, at least in part through stimulating angiogenesis and increasing the levels of the NF-κB-dependent chemokines CXCL1, CXCL2, and CXCL4.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6246959 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

B7-H3 promotes colorectal cancer angiogenesis through activating the NF-κB pathway to induce VEGFA expression.

Project description:Tumor angiogenesis is a hallmark of cancer and is involved in the tumorigenesis of solid tumors. B7-H3, an immune checkpoint molecule, plays critical roles in proliferation, metastasis and tumorigenesis in diverse tumors; however, little is known about the biological functions and molecular mechanism underlying B7-H3 in regulating colorectal cancer (CRC) angiogenesis. In this study, we first demonstrated that the expression of B7-H3 was significantly upregulated and was positively associated with platelet endothelial cell adhesion molecule-1 (CD31) level in tissue samples from patients with CRC. In addition, a series of in vitro and in vivo experiments showed that conditioned medium from B7-H3 knockdown CRC cells significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs), whereas overexpression of B7-H3 had the opposite effect. Furthermore, B7-H3 promoted tumor angiogenesis by upregulating VEGFA expression. Recombinant VEGFA abolished the inhibitory effects of conditioned medium from shB7-H3 CRC cells on HUVEC angiogenesis, while VEGFA siRNA or a VEGFA-neutralizing antibody reversed the effects of conditioned medium from B7-H3-overexpressing CRC cells on HUVEC angiogenesis. Moreover, we verified that B7-H3 upregulated VEGFA expression and angiogenesis by activating the NF-κB pathway. Collectively, our findings identify the B7-H3/NF-κB/VEGFA axis in promoting CRC angiogenesis, which serves as a promising approach for CRC treatment.

| S-EPMC6978425 | biostudies-literature

P2X7R promotes angiogenesis and tumour-associated macrophage recruitment by regulating the NF-κB signalling pathway in colorectal cancer cells.

Project description:Overexpression of P2X7R has been observed in several tumours and is related to cancer advancement and metastasis. However, the role of P2X7R in colorectal cancer (CRC) patients is not well understood. In the current study, overexpression of P2X7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2X7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry. In this study, we found that overexpression of P2X7R increases in the in vivo growth of tumours. P2X7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2X7R up-regulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumour cells with P2X7R overexpression stimulated cytokines to recruit tumour-associated macrophage (TAMs) to increase the growth of tumours. We also found that the NF-κB signalling pathway is involved in P2X7R-induced cytokine up-regulation. P2X7R promotes NF-κB-dependent cytokine induction, which leads to TAM recruitment to control tumour growth and advancement and remodelling of the stroma. Our findings demonstrate that P2X7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.

| S-EPMC7521273 | biostudies-literature

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway.

Project description:BackgroundConstitutively activated nuclear factor kappa B (NF-κB) signalling plays vital roles in bladder urothelial carcinoma (BC) progression. We investigate the effect of receptor-interacting protein kinase 4 (RIPK4) on NF-κB activation and BC progression.MethodsThe expression of RIPK4 was examined in 25 cryopreserved paired bladder samples and 112 paraffin BC specimens. In vivo and in vitro assays were performed to validate effect of RIPK4 on NF-κB pathway-mediated BC progression.ResultsHigh expression of RIPK4 was observed in BC tissues and was an independent predictor for poor overall survival. Up or downregulating the expression of RIPK4 enhanced or inhibited, respectively, the migration and invasion of BC cells in vitro and in vivo. Mechanistically, RIPK4 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor-interacting protein (RIP) and NF-κB essential modulator (NEMO). RIPK4 also promoted nuclear localisation of NF-κB-p65, and maintained activation of NF-κB substantially, leading to upregulation of VEGF-A, ultimately promoting BC cell aggressiveness.ConclusionsOur data highlighted the molecular aetiology and clinical significance of RIPK4 in BC: upregulation of RIPK4 contributes to NF-κB activation, and upregulates VEGF-A, and BC progression. Targeting RIPK4 might represent a new therapeutic strategy to improve survival for patients with BC.

| S-EPMC6008479 | biostudies-literature

SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS.

Project description:The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1β, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway.

| S-EPMC8631293 | biostudies-literature

Interaction with tumor‑associated macrophages promotes PRL‑3‑induced invasion of colorectal cancer cells via MAPK pathway‑induced EMT and NF‑κB signaling‑induced angiogenesis.

Project description:Protein phosphatase of regenerating liver‑3 (PRL‑3) is considered to be metastasis‑associated phosphatase and is associated with a poor prognosis. Additionally, tumor‑associated macrophages (TAMs) participate in cancer progression. A previous study demonstrated that PRL‑3 promotes invasion and metastasis by inducing TAM infiltration. However, the underlying mechanism has not been elucidated. In the present study, western blot analysis, polymerase chain reaction, immunohistochemistry, ELISA, mouse model experiments and functional experiments were performed to confirm that the interaction between TAMs and colorectal cancer (CRC) cells induced epithelial‑mesenchymal transition (EMT)‑associated features in CRC cells by activating mitogen‑activated protein kinase (MAPK) pathways in TAMs and upregulating the expression of interleukin (IL)‑6 and IL‑8. The neutralization of IL‑6 and IL‑8 reduced EMT and the invasive and migratory abilities of CRC cells. Therefore, IL‑6 and IL‑8 were considered important factors in EMT, and in CRC invasion and metastasis. In addition, increased angiogenesis was observed after TAMs were co‑cultured with CRC cells that overexpress PRL‑3. Vascular endothelial growth factor‑A was significantly upregulated, and the nuclear factor‑κB (NF‑κB) signaling pathway was activated in CRC cells after co‑culture. Moreover, nude mice injected with CRC cells with high PRL‑3 expression levels tended to generate larger xenografts. Immunohistochemistry results from xenografted CRC cells overexpressing PRL‑3 also confirmed the activation of MAPK pathways in xenografts. Overall, the findings indicate that PRL‑3 promotes CRC cell invasion and metastasis by activating MAPK pathways in TAMs to initiate the EMT, and PRL‑3 promotes angiogenesis by activating the NF‑κB pathway in CRC cells.

| S-EPMC6448091 | biostudies-literature

Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway.

Project description:Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, the identification of predictive biomarkers is necessary to effectively generate therapeutic strategies for metastatic human colorectal cancer (CRC). This study aims to identify how cells acquire resistance to anticancer drugs and whether the downregulation of miR-4454 is associated with the progression of CRC. Here, we have shown that the overexpression of miR-4454 in resistant tumors is a crucial precursor for the posttranscriptional repression of GNL3L in human chemoresistant CRC progression, and we used doxycycline induced miR-4454 overexpression that significantly reduced tumor volume in a subcutaneous injection nude mice model. Together, these observations highlight that the downregulation of miR-4454 in resistant clones is prominently responsible for maintaining their resistance against anticancer drug therapy. Our study indicates that the development of miR-4454 as a microRNA-based therapeutic approach to silence GNL3L may remarkably reduce oncogenic cell survival that depends on GNL3L/NF-κB signaling, making miR-4454 a candidate for treating metastatic human CRC.

| S-EPMC7281507 | biostudies-literature

DNMT1-induced miR-378a-3p silencing promotes angiogenesis via the NF-κB signaling pathway by targeting TRAF1 in hepatocellular carcinoma.

Project description:BackgroundAngiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). According to previous studies, miR-378a participates in tumorigenesis and tumor metastasis, but its exact role in HCC angiogenesis remains poorly understood.MethodsqRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by Cell Counting Kit-8 (CCK-8), Transwell, tube formation and Matrigel plug assays, RNA sequencing, bioinformatics, luciferase reporter, immunofluorescence and chromatin immunoprecipitation (ChIP) assays were used to detect the molecular mechanism by which miR-378a-3p inhibits angiogenesis.ResultsWe confirmed that miR-378a-3p expression was significantly downregulated and associated with higher microvascular density (MVD) in HCC; miR-378a-3p downregulation indicated a short survival time in HCC patients. miR-378a-3p knockdown led to a significant increase in angiogenesis in vitro and in vivo. We found that miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then downregulated secreted vascular endothelial growth factor. DNA methyltransferase 1 (DNMT1)-mediated hypermethylation of miR-378a-3p was responsible for downregulating miR-378a-3p. Moreover, a series of investigations indicated that p65 initiated a positive feedback loop that could upregulate DNMT1 to promote hypermethylation of the miR-378a-3p promoter.ConclusionOur study indicates a novel DNMT1/miR-378a-3p/TRAF1/NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.

| S-EPMC8576931 | biostudies-literature

CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer.

Project description:Chemokines and chemokine receptors are causally involved in the metastasis of human malignancies. As a crucial chemokine receptor for mediating immune homeostasis, however, the role of CCR4 in colorectal cancer (CRC) remains unknown. In this study, we found that high expression of CCR4 in CRC tissues was correlated with shorter overall survival and disease free survival. In vitro and in vivo experiments revealed that silencing CCR4 attenuated the invasion and metastasis of CRC cells, whereas ectopic overexpression of CCR4 contributed to the forced metastasis of these cells. We further demonstrated that matrix metalloproteinase 13 (MMP13) played an important role in CCR4-mediated cancer cell invasion, which is up-regulated by ERK/NF-κB signaling. Positive correlation between CCR4 and MMP13 expression was also observed in CRC tissues. Moreover, our investigations showed that the level of CCR4 could be induced by TNF-α dependent of NF-κB activation in CRC cells. CCR4 might be implicated in TNF-α-regulated cancer cells metastasis. Combination of CCR4 and TNF-α is a more powerful prognostic marker for CRC patients. These findings suggest that CCR4 facilitates metastasis through ERK/NF-κB/MMP13 signaling and acts as a downstream target of TNF-α. CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis.

| S-EPMC5216967 | biostudies-literature

TRIM31 promotes glioma proliferation and invasion through activating NF-κB pathway.

Project description:BackgroundGlioma is the most lethal primary brain tumor, the survival rate still isn't improved in the past decades. It's essential to study the regulatory mechanism of glioma progression, hoping to find new therapy targets or methods. The family of tripartite motif (TRIM) containing proteins are E3 ubiquitination ligases, which play critical role in various tumor progression.MethodsCell proliferation and invasion were analyzed by colony formation assay, soft agar growth assay, BrdU incorporation assay and transwell invasion assay. Luciferase reporter analysis was used to analyze NF-κB pathway activity.ResultsWe found TRIM31 was upregulated in glioma cells and tissues, its overexpression significantly promoted glioma cell proliferation and invasion, while its knockdown significantly inhibited glioma cell proliferation and invasion. Mechanism analysis found TRIM31 promoted NF-κB pathway activity and increased its targets expression. NF-κB inhibition reversed the phenotype caused by TRIM31, confirming TRIM31 promoted glioma progression through activating NF-κB pathway. Using clinical specimens found TRIM31 expression was positively correlative with NF-κB activity.ConclusionThis study found TRIM31 promoted glioma proliferation and invasion through activating NF-κB activity.

| S-EPMC6441556 | biostudies-literature

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway.

Project description:Macrophages act as the first immune defense line of the host against Mycobacterium tuberculosis (Mtb). A previous study showed that circRNA_SLC8A1 was significantly upregulated in Mtb-infected macrophages, but its regulatory mechanism in anti-tuberculosis infection is unclear. Therefore, this study aimed to investigate the role of circRNA_SLC8A1 in the anti-tuberculosis activity of macrophages. We showed that circRNA_SLC8A1 was upregulated in tuberculosis patients. Moreover, the binding sites of miR-20b-5p on circRNA_SLC8A1 and Sequestosome 1 (SQSTM1/p62) mRNA were predicted by StarBase and verified by the double luciferase reporter gene assay. Next, we found that miR-20b-5p expression was decreased, while SQSTM1 protein expression was increased in a time- and dose-dependent manner in the human macrophage U937 in response to Mtb infection. Furthermore, circRNA_SLC8A1 overexpression vector (circRNA_SLC8A1) or shRNA (sh-circRNA_SLC8A1) and/or miR-20b-5p mimic or inhibitor and/or SQSTM1 overexpression vector (SQSTM1) or small interfering RNA (si-SQSTM1) or its corresponding control were transfected into Mtb-infected macrophages. Results showed that overexpression of circRNA_SLC8A1 or miR-20b-5p inhibitor promoted the secretion of pro-inflammatory factors IL-1β, IL-6, and TNF-α, increased Nitric Oxide (NO) content and inducible nitric oxide synthase (iNOS) expression, inhibited Reactive oxygen species (ROS) production. Cleaved-caspase-3 protein expression, and cell apoptosis, and promoted Mtb survival. Silencing SQSTM1 inhibited secretion of pro-inflammatory factors and activation of the NF-κB pathway. Overexpression of miR-20b-5p blocked the promoting of circ-SLC8A1 on SQSTM1 protein expression. In summary, circRNA_SLC8A1 sponged miR-20b-5p to upregulate SQSTM1/p62 expression and promoted Mtb survival in macrophages through the NF-κB signaling pathway.

| S-EPMC10909944 | 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