Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PSMC5 Promotes Proliferation and Metastasis of Colorectal Cancer by Activating Epithelial-Mesenchymal Transition Signaling and Modulating Immune Infiltrating Cells.

ABSTRACT: We designed the present study to access the roles and mechanisms of PSMC5 in colorectal cancer (CRC). Transcriptomic and clinical data from public datasets and our center were retrospectively analyzed. Functional assays were performed to investigate the effects of PSMC5 on CRC cells. The results showed that PSMC5 was significantly higher in cancer than normal tissues. Moreover, patients with higher expression of PSMC5 showed poorer prognosis. Silencing of PSMC5 dramatically suppressed the proliferation and invasion of CRC cells, while overexpression led to the opposite. In addition, we screened downstream targets and found that PSMC5 regulates multiple pathways including epithelial-mesenchymal transition, hypoxia, and immune response. Consistently, we found that PSMC5 was negatively correlated with levels of CD8 + T cells and B cells while promoting infiltration of macrophages and neutrophils. Collectively, these findings suggested that PSMC5 was a promising biomarker and target for immune therapy for CRC.

SUBMITTER: He Z

PROVIDER: S-EPMC8323717 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

RAD18 promotes colorectal cancer metastasis by activating the epithelial?mesenchymal transition pathway.

Project description:RAD18 is an E3 ubiquitin?protein ligase that has a role in carcinogenesis and tumor progression owing to its involvement in error?prone replication. Despite its significance, the function of RAD18 has not been fully examined in colorectal cancer (CRC). In the present research, by collecting clinical samples and conducting immunohistochemical staining, we found that RAD18 expression was significantly increased in the CRC tissue compared with that noted in the adjacent non?cancerous normal tissues and that high expression of RAD18 was associated with lymph node metastasis and poor prognosis in CRC patients. In vitro, as determined by cell transfection, scratch, and Transwell experiments, it was also demonstrated that RAD18 increased the invasiveness and migration capacity of CRC cells (HCT116, DLD?1, SW480). The signaling pathway was analyzed by western blotting and the clinical data were analyzed by immunohistochemical staining and RT?PCR, indicating that the process of epithelial?mesenchymal transition (EMT) may be involved in RAD18?mediated migration and invasion of CRC cells. All of the above data indicate that RAD18 is a novel prognostic biomarker that may become a potential therapeutic target for CRC in the future.

| S-EPMC7251712 | biostudies-literature

CYR61 promotes colorectal carcinoma progression via activating epithelial-mesenchymal transition.

Project description:Colorectal carcinoma is the third most common type of cancer. Although the role of matricellular proteins and their association with tumor progression is well documented, limited data are available concerning their involvement in colorectal cancer. The current study investigated the expression pattern of matricellular proteins SPARC and CYR61 with epithelial-mesenchymal transition proteins in human CRC tissues and unleashed their association with colorectal cancer progression. The expression of these proteins was associated with advancement in tumor staging, nodal metastasis, and vascular invasion. Elevated CYR61 protein levels were also consistent with higher mesenchymal markers ZEB1 and Vimentin in collected biopsies and CRC cells. Moreover, expression of CYR61 promoted CRC cell migration, invasion, proliferation, and apoptosis. Our findings conclusively revealed the significant involvement of CYR61 in CRC progression through activating epithelial-mesenchymal transition. This discovery holds great promise for advancing therapeutic approaches in the treatment of CRC.

| S-EPMC10636662 | biostudies-literature

PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition.

Project description:Dysregulation of protein tyrosine phosphatase, receptor type B (PTPRB) correlates with the development of a variety of tumors. Here we show that PTPRB promotes metastasis of colorectal cancer (CRC) cells via inducing epithelial-mesenchymal transition (EMT). We find that PTPRB is expressed at significantly higher levels in CRC tissues compared to adjacent nontumor tissues and in CRC cell lines with high invasion. PTPRB knockdown decreased the number of invasive CRC cells in an in vitro wound healing model, and also reduced tumor metastasis in vivo. Conversely, PTPRB overexpression promoted CRC cell invasion in vitro and metastasis in vivo. PTPRB overexpression decreased vimentin expression and promoted E-cadherin expression, consistent with promotion of EMT, while PTPRB knockdown had the opposite effect. Hypoxic conditions induced EMT and promoted invasion in CRC cells, but these effects were eliminated by PTPRB knockdown. EMT blockade via TWIST1 knockdown inhibited the migration and invasiveness of CRC cells, and even increased PTPRB expression could not reverse this effect. Altogether, these data support the conclusion that PTPRB promotes invasion and metastasis of CRC cells via inducing EMT, and that PTPRB would be a novel therapeutic target for the treatment of CRC.

| S-EPMC6491493 | biostudies-literature

FOXF1 Induces Epithelial-Mesenchymal Transition in Colorectal Cancer Metastasis by Transcriptionally Activating SNAI1.

Project description:Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms of FOXF1 in the regulation of the progression of colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up-regulated in 93 paraffin-embedded archived human CRC tissue, and both high expression and nuclear location of FOXF1 were significantly associated with the aggressive characteristics and poorer survival of CRC patients. The GSEA analysis showed that the higher level of FOXF1 was positively associated with an enrichment of EMT gene signatures, and exogenous overexpression of FOXF1 induced EMT by transcriptionally activating SNAI1. Exogenous overexpression FOXF1 functionally promoted invasion and metastasis features of CRC cells, and inhibition of SNAI1 attenuates the invasive phenotype and metastatic potential of FOXF1-overexpressing CRC cells. Furthermore, the results of the tissue chip showed that the expression of FOXF1 was positively correlated with SNAI1 in CRC tissues chip. These results suggested that FOXF1 plays a critical role in CRC metastasis by inducing EMT via transcriptional activation of SNAI1, highlighting a potential new therapeutic strategy for CRC.

| S-EPMC6134153 | biostudies-literature

MicroRNA-21 promotes cell metastasis in cervical cancer through modulating epithelial-mesenchymal transition.

Project description:MicroRNA (miR)-21 is known to act as an oncogene in cervical cancer by promoting cell proliferation and migration; however, the underlying molecular mechanisms have remained to be fully elucidated. The present study revealed that the gene expression levels of miR-21 and epithelial-mesenchymal transition (EMT)-associated transcription factor Zinc finger E-box-binding homeobox 1 (ZEB1), in cervical cancer and lymphatic metastatic carcinoma tissues were significantly higher than those in normal tissues (P<0.05). Furthermore, the gene expression levels of miR-21 and ZEB1 were positively associated with muscular infiltration depth, parametrical invasion and lymph node metastasis in patients with cervical cancer. Immunohistochemistry assays indicated that the expression levels of ZEB1 and the mesenchymal cell marker Vimentin in cervical cancer tissues were significantly higher than those in normal cervical tissues (P<0.05). Overexpression of miR-21 in HeLa and SiHa cells caused the upregulation of the mesenchymal cell markers Vimentin and N-cadherin, and downregulation of the epithelial cell marker E-cadherin at the proteins level. In addition, overexpression of miR-21 enhanced the invasiveness of HeLa and SiHa cells. These results demonstrated that miR-21 was upregulated in cervical cancer tissues and promoted cell metastasis through modulating EMT. A better understanding of the role of miR-21 and EMT may lead to the development of more effective therapies for patients with cervical cancer.

| S-EPMC7074379 | biostudies-literature

Goosecoid promotes the metastasis of hepatocellular carcinoma by modulating the epithelial-mesenchymal transition.

Project description:The homeobox gene, goosecoid (GSC), is a transcription factor that participates in cell migration during embryonic development. Because cell migration during development has characteristics similar to cell invasion during metastasis, we evaluated the potential role of GSC in the metastasis of hepatocellular carcinoma (HCC). GSC expression in HCC cell lines and tissues was evaluated, and its effects on the migration potential of HCC cells were determined by GSC knock-down and overexpression methods. In addition, the prognostic role of GSC expression in the metastasis of cancer cells in HCC patients was determined. Our data showed that GSC was highly expressed in several HCC cell lines, particularly in a highly metastatic HCC cell line. Overexpression of GSC promoted cell migration and invasion of HCC cells in vitro. Gain-of-function induced the epithelial-mesenchymal transition but not collective cell migration, whereas loss-of-function induced the reverse change. High-level expression of GSC correlated closely with poor survival and lung metastasis in HCC patients; lung metastases showed more upregulated GSC expression than the primary tumor. We conclude that GSC promotes metastasis of HCC potentially through initiating the epithelial-mesenchymal transition. GSC is also a prognostic factor for poor survival and metastasis of HCC, which suggests its potential as a therapeutic target for metastatic HCC.

| S-EPMC4208742 | biostudies-literature

ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer.

Project description:The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.

| S-EPMC7142079 | biostudies-literature

USP22 drives colorectal cancer invasion and metastasis via epithelial-mesenchymal transition by activating AP4.

Project description:Ubiquitin specific peptidase 22 (USP22), a putative cancer stem cell marker, is overexpressed in liver metastases of colorectal cancer (CRC). However, the mechanism by which USP22 promotes CRC metastasis remains largely unknown. Here, we report that USP22 and AP4 are simultaneously overexpressed during TGF-?1-induced CRC cell epithelial-mesenchymal transition (EMT). USP22 up-regulation enhances CRC cell migration and invasion and EMT-related marker and AP4 expression, but these effects are partly blocked by AP4 knockdown. In addition, USP22 binds to the promoter region of AP4 to activate its transcription. In vivo, elevated USP22 expression promotes CRC cell metastasis to the lungs in nude mice, as evidenced by the fact that CRC metastatic nodules stain deeply positive for USP22 and AP4. In human CRC tissues, the genes encoding USP22 and AP4 are overexpressed in metastatic liver lesions compared with primary cancer tissues, and their overexpression is significantly associated with poor CRC patient survival. These findings indicate that USP22 and AP4 may serve as prognostic markers for predicting the risk of developing distant metastases in CRC.

| S-EPMC5464819 | biostudies-other

miR-10a suppresses colorectal cancer metastasis by modulating the epithelial-to-mesenchymal transition and anoikis.

Project description:MicroRNAs (miRNAs) have a critical role in tumorigenesis and metastasis, which are major obstacles of cancer therapy. However, the role of miRNAs in colorectal cancer (CRC) metastasis remains poorly understood. Here, we found that miRNA-10a (miR-10a) was upregulated in primary CRC tissues and cell line (SW480) derived from primary CRC compared with metastatic cancer tissues in lymph node and cell line (SW620). The differential expression of miR-10a was inversely correlated with distant metastasis and invasion depth. miR-10a promoted migration and invasion in vitro but inhibited metastasis in vivo by regulating the epithelial-to-mesenchymal transition and anoikis. Furthermore, matrix metalloproteinase 14 (MMP14) and actin gamma 1 (ACTG1) were validated as target genes of miR-10a in CRC cells. Ectopic expression of MMP14 and ACTG1 counteracted the decreased cell adhesion and anoikis resistance activities induced by miR-10a. These findings not only describe the mechanism by which miR-10a suppresses CRC metastasis but also suggest the potential prognostic and therapeutic value of miR-10a in CRC patients.

| S-EPMC5477594 | biostudies-literature

Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis.

Project description:Cyclin dependent kinase-3 (Cdk3) is a positive regulator of the G1 mammalian cell cycle phase. Cdk3 is involved in cancer progression, but very little is known about its mechanism in cancer development and progression. Herein, we found that Cdk3 increased colorectal cancer metastasis through promoting epithelial-mesenchymal transition (EMT) shift. Cdk3 was found to highly express in metastatic cancer and induce cell motility and invasion. Cdk3 was shown to phosphorylate c-Jun at Ser 63 and Ser 73 in vitro and ex vivo. Cdk3-phosphorylated c-Jun at Ser 63 and Ser 73 resulted in an increased AP-1 activity. Ectopic expression of Cdk3 promoted colorectal cancer from epithelial to mesenchymal transition conjugating AP-1 activation, while AP-1 inhibition dramatically decreased Cdk3-increased EMT shift. These results showed that the Cdk3/c-Jun signaling axis mediating epithelial-mesenchymal transition plays an important role in colorectal cancer metastasis.

| S-EPMC4872765 | 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