Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HMGA1 promotes gastric cancer growth and metastasis by transactivating SUZ12 and CCDC43 expression.

ABSTRACT: HMGA1 protein is an architectural transcription factor that has been implicated in the progression of multiple malignant tumors. However, the role of HMGA1 in the growth and metastasis of gastric cancer (GC) has not yet been elucidated. Here, we show that HMGA1 is overexpressed in GC cells and the high expression of HMGA1 was correlated with worse survival in GC patients using a bioinformatics assay. Functionally, HMGA1 affected the EdU incorporation, colony formation, migration and invasion of GC cells by exogenously increasing or decreasing the expression of HMGA1. Mechanistically, HMGA1 directly bound to the SUZ12 and CCDC43 promoter and transactivated its expression in GC cells. Inhibition of SUZ12 and CCDC43 attenuated the proliferation, migration and invasiveness of HMGA1-overexpressing GC cells in vitro. Moreover, both HMGA1 and SUZ12/CCDC43 were highly expressed in cancer cells but not in normal gastric tissues, and their expressions were positively correlated. Finally, a tail vein metastatic assay showed that HMGA1 promoted SUZ12/CCDC43-mediated GC cell metastasis in vivo. Our findings suggest that HMGA1 promotes GC growth and metastasis by transactivating SUZ12 and CCDC43 expression, highlighting HMGA1 as a potential prognostic biomarker in the treatment of GC.

SUBMITTER: Yang Q

PROVIDER: S-EPMC8266323 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

HMGA1 Promotes Hepatic Metastasis of Colorectal Cancer by Inducing Expression of Glucose Transporter 3 (GLUT3).

Project description:BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide, and more than half of CRC patients have CRC liver metastasis (CRCLM). Mounting evidence indicates that high mobility group protein A1(HMGA1) is overexpressed in many cancer types, but its role in CRCLM has been obscure. MATERIAL AND METHODS Using immunohistochemistry, we assessed the expression of HMGA1 in 73 patients with CRCLM, and compared HMGA1 mRNA in 17 pairs of CRCs, CRCLM tissues, and normal liver tissues. The clinical significance of HMGA1 was evaluated by analyzing its correlation with the clinicopathological factors and overall survival (OS) rates. The function of HMGA1 in CRC invasion was investigated and the underlying mechanism of HMGA1-induced invasion was explored with in vitro experiments. RESULTS In CRCLMs, the high-HMGA1 and low-HMGA1 patients accounted for 53.42% and 46.58% of all patients, respectively. High HMGA1 expression in CRCLM was significantly associated with low OS rates. In vitro experiments demonstrated that HMGA1 promoted glucose transporter 3 (GLUT3) transcription and expression in CRC cells. GLUT3 was required in HMGA1-involved invasion, and GLUT3 expression was associated with poor prognosis of CRCLM. CONCLUSIONS High HMGA1 and GLUT3 expression in CRCLM was significantly correlated with poor prognosis of CRCLM. HMGA1 promoted CRC invasion by elevating GLUT3 transcription and expression.

| S-EPMC7532698 | biostudies-literature

NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells.

Project description:NANOGP8 is one of the NANOG pseudogenes and is expressed together with NANOG in multiple tumor tissues and cell lines. The biological functions of NANOGP8 in progression of gastric cancer are unclear. In the present study, the role of NANOGP8 was investigated in gastric cancer cells. The gathered data demonstrated that NANOG expression in both mRNA and protein was elevated in gastric cancer cell lines relative to a normal gastric epithelial cell line. Downregulation of NANOGP8 inhibited cell proliferation and increased apoptosis in human gastric carcinoma cell lines. Furthermore, silencing of NANOGP8 suppressed tumor growth in vivo. Interestingly, it was identified that deleted in breast cancer 1 (DBC1) expression was also markedly downregulated following NANOGP8 knockdown. DNA microarray and dual-luciferase assays further indicated that NANOGP8 may bind to the DBC1 promoter region and regulate DBC1 expression. Therefore, the gathered data provided evidence that NANOGP8 contributes to progression of gastric cancer via DBC1 and may have potential translational significance.

| S-EPMC6313168 | biostudies-literature

circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/β-catenin signaling.

Project description:Colorectal cancer (CRC) is one of the most common and deadly cancers, and the incidence of CRC is on the rise. Due to the lack of early diagnosis method and high metastasis of the disease, the prognosis of CRC remains very poor. Exploring the underlying molecular mechanisms of CRC is very necessary for effective therapy. In this study, we investigated the function of circBANP in CRC. The results showed that circBANP was elevated in both CRC tissues and cells and its level positively correlated with the stage of CRC. Knockdown of circBANP greatly suppressed the epithelial-mesenchymal transition (EMT) process and CRC cell proliferation, migration, and invasion. In addition, knockdown of circBANP inhibited CRC tumor growth and metastasis in vivo. Further, circBANP directly bound to let-7d-5p and regulated CRC development via acting as a let-7d-5p sponge. Let-7d-5p directly targeted HMGA1 and thus circBANP/let-7d-5p regulated Wnt/β-catenin signaling via HMGA1. Collectively, circBANP promotes CRC development and metastasis via acting as a let-7d-5p sponge to regulate HMGA1/Wnt/β-catenin signaling, providing a potential biomarker and therapeutic target for the management of CRC.

| S-EPMC8079336 | biostudies-literature

Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma

Project description:Cholangiocarcinomas (CCAs) are rare but aggressive tumors of the bile ducts. CCAs are often diagnosed at an advanced stage and respond poorly to current conventional radiotherapy and chemotherapy. High mobility group A1 (HMGA1) is an architectural transcription factor that is overexpressed in multiple malignant tumors. In this study, we showed that the expression of HMGA1 is frequently elevated in CCAs and that the high expression of this gene is associated with a poor prognosis. Functionally, HMGA1 promotes CCA cell proliferation/invasion and xenograft tumor growth. Furthermore, HMGA1 transcriptionally activates RAD51 by binding to its promoter through two HMGA1 response elements. Notably, overexpression of HMGA1 promotes radioresistance whereas its knockdown causes radiosensitivity of CCA cells to X-ray irradiation. Moreover, rescue experiments reveal that inhibition of RAD51 reverses the effect of HMGA1 on radioresistance and proliferation/invasion. These findings suggest that HMGA1 functions as a novel regulator of RAD51 and confers radioresistance in cholangiocarcinoma.

| S-EPMC8556338 | biostudies-literature

The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2.

Project description:Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3'UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.

| S-EPMC8290256 | biostudies-literature

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer.

Project description:Gastric cancer is one of the major malignancies with poor survival outcome. In this study, we reported that NUDT21 promoted cell proliferation, colony formation, cell migration and invasion in gastric cancer cells. The expression levels of NUDT21 were found to be much higher in human gastric cancer tissues compared with normal gastric tissues. NUDT21 expression was positively correlated with tumor size, lymph node metastasis and clinical stage in gastric cancer patients. High level of NUDT21 was associated with poor overall survival (OS) rates in gastric cancer patients. The expression levels of NUDT21 were also much higher in gastric cancer tissues from patients with tumor metastasis compared with those of patients without tumor metastasis. Moreover, forced expression of NUDT21 in gastric cancer cells promoted tumor growth and cell proliferation in xenograft nude mice, and depletion of NUDT21 in gastric cancer cells restrained lung metastasis in vivo. Through high throughput RNA-sequencing, SGPP2 was identified to be positively regulated by NUDT21 and mediated the tumor promoting role of NUDT21 in gastric cancer cells. Therefore, NUDT21 played an oncogenic role in human gastric cancer cells. NUDT21 could be considered as a novel potential target for gastric cancer therapy.

| S-EPMC8514838 | biostudies-literature

Knockdown of HMGA1 inhibits human breast cancer cell growth and metastasis in immunodeficient mice.

Project description:The high mobility group A1 gene (HMGA1) has been previously implicated in breast carcinogenesis, and is considered an attractive target for therapeutic intervention because its expression is virtually absent in normal adult tissue. Other studies have shown that knockdown of HMGA1 reduces the tumorigenic potential of breast cancer cells in vitro. Therefore, we sought to determine if silencing HMGA1 can affect breast cancer development and metastatic progression in vivo. We silenced HMGA1 expression in the human breast cancer cell line MDA-MB-231 using an RNA interference vector, and observed a significant reduction in anchorage-independent growth and tumorsphere formation, which respectively indicate loss of tumorigenesis and self-renewal ability. Moreover, silencing HMGA1 significantly impaired xenograft growth in immunodeficient mice, and while control cells metastasized extensively to the lungs and lymph nodes, HMGA1-silenced cells generated only a few small metastases. Thus, our results show that interfering with HMGA1 expression reduces the tumorigenic and metastatic potential of breast cancer cells in vivo, and lend further support to investigations into targeting HMGA1 as a potential treatment for breast cancer.

| S-EPMC3662800 | biostudies-other

Nicotinamide nucleotide transhydrogenase-mediated redox homeostasis promotes tumor growth and metastasis in gastric cancer.

Project description:Overcoming oxidative stress is a critical step for tumor growth and metastasis, however the underlying mechanisms in gastric cancer remain unclear. In this study, we found that overexpression of nicotinamide nucleotide transhydrogenase (NNT) was associated with shorter overall and disease free survival in gastric cancer. The NNT is considered a key antioxidative enzyme based on its ability to regenerate NADPH from NADH. Knockdown of NNT caused significantly NADPH reduction, induced high levels of ROS and significant cell apoptosis under oxidative stress conditions such as glucose deprival and anoikis. In vivo experiments showed that NNT promoted tumor growth, lung metastasis and peritoneal dissemination of gastric cancer. Moreover, intratumoral injection of NNT siRNA significantly suppressed gastric tumor growth in patient-derived xenograft (PDX) models. Overall, our study highlights the crucial functional roles of NNT in redox regulation and tumor progression and thus raises an important therapeutic hypothesis in gastric cancer.

| S-EPMC6079569 | biostudies-literature

ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling.

Project description:ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.

| S-EPMC8436930 | biostudies-literature

HDAC4 promotes the growth and metastasis of gastric cancer via autophagic degradation of MEKK3.

Project description:BackgroundHistone deacetylases (HDACs) have been shown to be involved in tumorigenesis, but their precise role and molecular mechanisms in gastric cancer (GC) have not yet been fully elucidated.MethodsBioinformatics screening analysis, qRT-PCR, and immunohistochemistry (IHC) were used to identify the expression of HDAC4 in GC. In vitro and in vivo functional assays illustrated the biological function of HDAC4. RNA-seq, GSEA pathway analysis, and western blot revealed that HDAC4 activated p38 MAPK signalling. Immunofluorescence, western blot, and IHC verified the effect of HDAC4 on autophagy. ChIP and dual-luciferase reporter assays demonstrated that the transcriptional regulation mechanism of HDAC4 and ATG4B.ResultsHDAC4 is upregulated in GC and correlates with poor prognosis. In vitro and in vivo assays showed that HDAC4 contributes to the malignant phenotype of GC cells. HDAC4 inhibited the MEF2A-driven transcription of ATG4B and prevented MEKK3 from p62-dependent autophagic degradation, thus activating p38 MAPK signalling. Reciprocally, the downstream transcription factor USF1 enhanced HDAC4 expression by regulating HDAC4 promoter activity, forming a positive feedback loop and continuously stimulating HDAC4 expression and p38 MAPK signalling activation.ConclusionHDAC4 plays an oncogenic role in GC, and HDAC4-based targeted therapy would represent a novel strategy for GC treatment.

| S-EPMC9296555 | 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