Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.

ABSTRACT: Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.

SUBMITTER: Yan Q

PROVIDER: S-EPMC8711721 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Keratin19 promotes pancreatic cancer progression and poor prognosis via activating the Hedgehog pathway.

Project description:Pancreatic cancer is a serious threat to human health, with strong invasiveness, rapid progression and poor prognosis. Tumors expressing keratin 19 (K19) have stronger invasiveness and a worse prognosis. However, the role and mechanism of K19 in pancreatic cancer have remained largely elusive. In the present study, K19 expression was detected in pancreatic cancer tissues, its effect on proliferation, apoptosis and metastasis of pancreatic cancer at the cellular, in vivo preclinical and clinical levels was evaluated and its effect on the Hedgehog pathway was analyzed. K19 was significantly overexpressed in pancreatic cancer, promoted pancreatic cancer proliferation and metastasis, inhibited tumor cell apoptosis and was associated with poor prognosis. Mechanistically, these effects were mediated through the activation of the Hedgehog pathway. In conclusion, K19 may be a novel target molecule for pancreatic cancer treatment.

| S-EPMC9946805 | biostudies-literature

Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression.

Project description:Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed. Furthermore, RAB5 suppression analysis by siRNA was performed to determine the roles of RAB5 in morphological change, proliferation potency, cell migration ability, and invasiveness of the pancreatic cancer cell line.High RAB5 expression correlated with the presence of lymphatic invasion and venous invasion and low E-cadherin expression. Patients with high RAB5 expression had a poorer prognosis than those with low RAB5 expression. RAB5 suppression in pancreatic cancer cells enhanced E-cadherin expression; changed cell morphology from spindle to round; and inhibited proliferation, invasion, and cell migration.RAB5 contributes to poor prognosis and progression in pancreatic cancer patients. It may be a promising candidate for individualized therapy in refractory pancreatic cancer.

| S-EPMC5355344 | biostudies-literature

Reduced FBXW7 expression in pancreatic cancer correlates with poor prognosis and chemotherapeutic resistance via accumulation of MCL1.

Project description:Pancreatic cancer is a highly malignant tumor type with poor outcomes, and elucidation of the mechanisms involved in cancer progression and therapeutic resistance is critical. FBXW7 is a key regulator of tumor malignant potential, and its substrate MCL1 regulates therapeutic resistance in human malignancies. Therefore, determination of the relevance of FBXW7 expression is critical for improving patient outcomes. In this study, we investigated the function and clinical significance of FBXW7 in pancreatic cancer. FBXW7 expression was evaluated by immunohistochemistry in 122 pancreatic cancer tissues. Reduced FBXW7 expression was significantly associated with advanced venous invasion, high MCL1 expression, enhanced Ki-67 expression, and poor prognosis and was an independent poor prognostic factor. Among patients who underwent gemcitabine treatment after surgery, reduced FBXW7 expression was also significantly associated with poor prognosis. Knockdown of FBXW7 in vitro enhanced cell proliferation, and migration, and invasion abilities and promoted gemcitabine and nab-paclitaxel chemoresistance in pancreatic cancer cells. Moreover, FBXW7-knockdown cells showed accumulation of MCL1, and the enhanced chemoresistance observed in FBXW7-knockdown cells was eliminated by MCL1 suppression. These results suggested that FBXW7 was associated with cancer progression and mediated sensitivity to gemcitabine and nab-paclitaxel via MCL1 accumulation in pancreatic cancer. Thus, the FBXW7/MCL1 axis may be a promising therapeutic tool to overcome refractory pancreatic cancer.

| S-EPMC5762537 | biostudies-literature

Upregulation of CENP-H in tongue cancer correlates with poor prognosis and progression.

Project description:BACKGROUND: Centromere protein H (CENP-H) is one of the fundamental components of the human active kinetochore. Recently, CENP-H was identified to be associated with tumorigenesis. This study was aimed to investigate the clinicopathologic significance of CENP-H in tongue cancer. METHODS: RT-PCR, real time RT-PCR and Western blot were used to examine the expression of CENP-H in tongue cancer cell lines and biopsies. CENP-H protein level in paraffin-embedded tongue cancer tissues were tested by immunohistochemical staining and undergone statistical analysis. CENP-H-knockdown stable cell line was established by infecting cells with a retroviral vector pSuper-retro-CENP-H-siRNA. The biological function of CENP-H was tested by MTT assay, colony formation assay, and Bromodeoxyuridine (BrdU) incorporation assay. RESULTS: CENP-H expression was higher in tongue cancer cell lines and cancer tissues (T) than that in normal cell and adjacent noncancerous tongue tissues (N), respectively. It was overexpressed in 55.95% (94/168) of the paraffin-embedded tongue cancer tissues, and there was a strong correlation between CENP-H expression and clinical stage, as well as T classification. CENP-H can predict the prognosis of tongue cancer patients especially those in early stage. Depletion of CENP-H can inhibit the proliferation of tongue cancer cells (Tca8113) and downregulate the expression of Survivin. CONCLUSION: These findings suggested that CENP-H involves in the development and progression of tongue cancer. CENP-H might be a valuable prognostic indicator for tongue cancer patients within early stage.

| S-EPMC2706220 | biostudies-other

NEK7 Promotes Pancreatic Cancer Progression And Its Expression Is Correlated With Poor Prognosis.

Project description:The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.

| S-EPMC8290842 | biostudies-literature

Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer Progression and Poor Prognosis.

Project description:PurposeUridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer.MethodsWe searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets.ResultsWe found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures.ConclusionThese findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.

| S-EPMC5500396 | biostudies-literature

Overexpression of thymosin β10 correlates with disease progression and poor prognosis in bladder cancer.

Project description:Thymosin β10 (TMSB10) has been found to be overexpressed and function as an oncogene in several types of cancer. However, there have been limited reports on the role of TMSB10 in bladder cancer (BCa). In the present study, reverse transcription-quantitative PCR was used to quantify the expression of TMSB10 in BCa cell lines, clinical specimens and their corresponding control samples. The protein expression of TMSB10 was also examined in archived tissues from 101 patients with pathologically confirmed BCa by immunohistochemistry. Univariate and multivariate Cox regression models were used to evaluate the prognostic significance of TMSB10 in patients with BCa. The data indicated that the mRNA levels of TMSB10 were significantly overexpressed in BCa cell lines. In addition, the protein levels of TMSB10 were overexpressed in BCa tissues compared with those in adjacent normal tissues. In 55/101 (54.5%) BCa specimens, high expression levels of TMSB10 were noted. Statistical analysis revealed that the high expression of TMSB10 was positively associated with muscular invasion (P<0.05). In addition, a high expression of TMSB10 was associated with shorter overall survival (OS) of patients (P<0.05; log-rank test). The univariate and multivariate analyses suggested that the protein overexpression of TMSB10 was an unfavorable prognostic factor for OS (P<0.05) in patients with BCa. Knockdown of the expression of TMSB10 significantly suppressed cell migration and invasion. In conclusion, TMSB10 can be considered an independent factor for the poor prognosis of patients with BCa. The targeting of TMSB10 can reduce the migration and invasion of BCa cells.

| S-EPMC6781816 | biostudies-literature

WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma.

Project description:There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott-Aldrich syndrome protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of the WASP family in cancer progression remains elusive. Here, we studied the role of WASP and SCAR Homolog (WASH), a recently identified WASP family member, in human esophageal squamous cell carcinoma (ESCC). Using three human ESCC cell lines, we found that WASH expression was significantly elevated in cancer stem-like cells enriched by sphere formation assay. WASH knockdown decreased the sphere-forming capacity of esophageal cancer cells whereas WASH over-expression exhibited the opposite effect. Mechanistically, we identified interleukin-8 (IL-8) as a key downstream target of WASH. IL-8 knockdown completely attenuated tumor sphere formation induced by WASH overexpression. WASH knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, high WASH levels were associated with poor clinical prognosis in a total of 145 human ESCC tissues. Collectively, our results suggest an essential role of the WASH/IL-8 pathway in human ESCC by maintaining the stemness of cancer cells. Hence, targeting this pathway might represent a promising strategy to control human esophageal carcinoma.

| S-EPMC5715296 | biostudies-literature

ERO1α promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer.

Project description:Pancreatic cancer is a leading cause of mortality worldwide due to the difficulty of detecting early-stage disease and our poor understanding of the mediators that drive progression of hypoxic solid tumors. We therefore used a heavy isotope 'pulse/trace' proteomic approach to determine how hypoxia (Hx) alters pancreatic tumor expression of proteins that confer treatment resistance, promote metastasis, and suppress host immunity. Using this method, we identified that hypoxia stress stimulates pancreatic cancer cells to rapidly translate proteins that enhance metastasis (NOTCH2, NCS1, CD151, NUSAP1), treatment resistance (ABCB6), immune suppression (NFIL3, WDR4), angiogenesis (ANGPT4, ERO1α, FOS), alter cell metabolic activity (HK2, ENO2), and mediate growth-promoting cytokine responses (CLK3, ANGPTL4). Database mining confirmed that elevated gene expression of these hypoxia-induced mediators is significantly associated with poor patient survival in various stages of pancreatic cancer. Among these proteins, the oxidoreductase enzyme ERO1α was highly sensitive to induction by hypoxia stress across a range of different pancreatic cancer cell lines and was associated with particularly poor prognosis in human patients. Consistent with these data, genetic deletion of ERO1α substantially reduced growth rates and colony formation by pancreatic cancer cells when assessed in a series of functional assays in vitro. Accordingly, when transferred into a mouse xenograft model, ERO1α-deficient tumor cells exhibited severe growth restriction and negligible disease progression in vivo. Together, these data indicate that ERO1α is potential prognostic biomarker and novel drug target for pancreatic cancer therapy.

| S-EPMC6800261 | biostudies-literature

Downregulation of PGM5 expression correlates with tumor progression and poor prognosis in human prostate cancer.

Project description:Prostate cancer (PCa) is the most common malignancy in men in developed countries. Prostate-specific antigen (PSA) remains the most widely used serum marker for prostate cancer. Here, we reported that the expression of phosphoglucomutase-like protein 5 (PGM5) is significantly lower in prostate cancer tissue. The low expression of PGM5 and its related gene signature were found to be linked to poor clinical outcome and high Gleason score. In vitro assays showed that overexpression of PGM5 significantly repressed proliferation and migration of prostate cancer cells. GO and pathway analyses showed the enrichment of genes in regulation of cell growth and migration, and pathways related in cancer. Our additional results showed that the downregulation of PGM5 is closely related to DNA methylation. Taken together, our findings provide the first evidence that PGM5 expression is associated with prostate cancer progression. These results also highlight a preclinical rationale that PGM5 represents a prognostic marker and a promising target for new therapeutic strategies in prostate cancer.

| S-EPMC9276915 | 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