Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Exocrine Differentiation and Proliferation Factor (EXDPF) Gene Promotes Ovarian Cancer Tumorigenesis by Up-Regulating DNA Replication Pathway.

ABSTRACT: The Exocrine Differentiation and Proliferation Factor (EXDPF) gene could promote exocrine while inhibit endocrine functions. Although it is well known that ovary is an endocrine organ, the functions of EXDPF in ovarian cancer development is still unknown. This study demonstrated that EXDPF gene is significantly higher expressed in ovarian tumors compared to normal ovarian tissue controls. EXDPF DNA amplification was exhibited in lots of human tumors including 7.19% of ovarian tumors. Also, high expression of EXDPF positively correlated with poor overall survival (OS) of ovarian cancer patients. EXDPF expression could be universally detected in most epithelial ovarian cancer cells (SKOV3, IGROV1, MACS, HO8910PM, ES2, COV362 and A2780) tested in this study. Knock-down of EXDPF by siRNA delivered by plasmid or lentivirus largely inhibited ovarian cancer cells, IGROV1 and SKOV3 proliferation, migration and tumorigenesis in vitro and/or in vivo. Knock-down of EXDPF sensitized SKOV3 cells to the treatment of the front-line drug, paclitaxel. Mechanism study showed that EXDPF enhanced DNA replication pathway to promote ovarian cancer tumorigenesis. In conclusion, this study demonstrated that EXDPF could be a potential therapeutic target as a pro-oncogene of ovarian cancer.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC8141798 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

MiR-26a promotes ovarian cancer proliferation and tumorigenesis.

Project description:MicroRNAs (miRNAs) important for posttranscriptional gene expression are involved in the initiation and progression of human cancer. In this study, we reported that miR-26a was over-expressed in human EOC specimens and the expression level of extracellular miR-26a in plasma can distinguish patients from healthy controls in EOC. Ectopic expression of miR-26a in ovarian cancer (OC) cells increased cell proliferation and clonal formation. This growth promoting effect of OC cell growth was mediated by miR-26a inhibition of the posttranscription of ER-?. Furthermore, inhibition of miR-26a suppressed the tumor formation generated by injecting OC cells in nude mice. Our results suggest that aberrantly expressed miR-26a may contribute to OC development.

| S-EPMC3899311 | biostudies-literature

TOP2A Promotes Tumorigenesis of High-grade Serous Ovarian Cancer by Regulating the TGF-?/Smad Pathway.

Project description:Background: High-grade serous ovarian cancer (HGS) is the most aggressive form of ovarian cancer due to its rapid spread, insidious onset, and early dissemination throughout the abdominal cavity. However, the molecular pathogenesis of HGS remains unclear. This study aimed to identify key pathogenic genes and explore the underlying molecular mechanisms of HGS using bioinformatics analysis and biological experiments. Methods: Two datasets were downloaded from the Gene Expression Omnibus databases to find differentially expressed genes (DEGs) between HGS and normal tissue samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were applied to investigate the primary functions of the DEGs. The protein-protein interaction network of the DEGs was constructed, and the interactions of various genes were ranked. Results: Topoisomerase II? (TOP2A) was identified as the hub gene associated with survival and mutation. Gene Set Enrichment Analysis and Gene Set Variation Analysis were conducted to predict the potential biological functions of TOP2A. Furthermore, the TOP2A expression level was significantly up-regulated in HGS cell lines, SKOV3 and HEY. Moreover, the proliferation, migration, and invasion capacities of SKOV3 and HEY cells were strongly suppressed after TOP2A knockdown. In addition, the levels of phosphorylated Smad2 and Smad3, the key members of the transforming growth factor-? (TGF-?)/Smad pathway that regulate HGS tumorigenesis, strongly decreased after knockdown of TOP2A. Conclusions: This study identified that TOP2A was up-regulated in HGS, and it accelerated HGS progression via the TGF-?/Smad pathway. The findings provided a blueprint for TOP2A serving as a therapeutic target and a treatment response prediction biomarker for HGS.

| S-EPMC7196274 | biostudies-literature

PARP10 promotes cellular proliferation and tumorigenesis by alleviating replication stress.

Project description:During carcinogenesis, cells are exposed to increased replication stress due to replication fork arrest at sites of DNA lesions and difficult to replicate genomic regions. Efficient fork restart and DNA repair are important for cancer cell proliferation. We previously showed that the ADP-ribosyltransferase PARP10 interacts with the replication protein proliferating cell nuclear antigen and promotes lesion bypass by recruiting specialized, non-replicative DNA polymerases. Here, we show that PARP10 is overexpressed in a large proportion of human tumors. To understand the role of PARP10 in cellular transformation, we inactivated PARP10 in HeLa cancer cells by CRISPR/Cas9-mediated gene knockout, and overexpressed it in non-transformed RPE-1 cells. We found that PARP10 promotes cellular proliferation, and its overexpression alleviates cellular sensitivity to replication stress and fosters the restart of stalled replication forks. Importantly, mouse xenograft studies showed that loss of PARP10 reduces the tumorigenesis activity of HeLa cells, while its overexpression results in tumor formation by non-transformed RPE-1 cells. Our findings indicate that PARP10 promotes cellular transformation, potentially by alleviating replication stress and suggest that targeting PARP10 may represent a novel therapeutic approach.

| S-EPMC6158756 | biostudies-literature

HADHA promotes ovarian cancer outgrowth via up-regulating CDK1

Project description: Not available

| S-EPMC10658966 | biostudies-literature

TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway.

Project description:The highly conserved protease TASP1 not only takes part in critical site-specific proteolysis, but also plays an important role in numerous liquid and solid malignancies. However, the TASP1 expression and its biological regulation function in malignant gallbladder carcinoma (GBC) remain fully unknown. Here we observed that TASP1 levels were substantially overexpressed in GBC samples compared with non-tumor tissues. High TASP1 level was closely associated with T stage and metastasis, and was also correlated with poor prognosis in GBC patients. The depletion of TASP1 inhibited GBC cell proliferation and metastasis in vitro and in vivo. Furthermore, we first revealed that FAM49B had biological function and was positively regulated by TASP1 activating PI3K/AKT signaling pathway in GBC. At the same time, FAM49B also promoted GBC cell proliferation and migration. Inhibition of PI3K/AKT with LY294002 or FAM49B expression abrogated Myc-TASP1/Lv-shTASP1-induced GBC cell proliferation and motility. In conclusion, these findings demonstrate that TASP1 is critical for GBC progression via TASP1-PI3K/AKT-FAM49B axis and it may be a novel prognostic factor. The therapeutic targeting TASP1 may be a potential treatment approach for GBC patients.

| S-EPMC7019140 | biostudies-literature

CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.

Project description:Cullin-RING ubiquitin ligases (CRLs) participate in the regulation of diverse cellular processes including cell cycle progression. Mutations in the X-linked CUL4B, a member of the cullin family, cause mental retardation and other developmental abnormalities in humans. Cells that are deficient in CUL4B are severely selected against in vivo in heterozygotes. Here we report a role of CUL4B in the regulation of replication licensing. Strikingly, CDC6, the licensing factor in replication, was positively regulated by CUL4B and contributed to the loading of MCM2 to chromatin. The positive regulation of CDC6 by CUL4B depends on CDK2, which phosphorylates CDC6, protecting it from APC(CDH1)-mediated degradation. Thus, aside being required for cell cycle reentry from quiescence, CDK2 also contributes to pre-replication complex assembly in G1 phase of cycling cells. Interestingly, the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2. Our findings thus establish a CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing.

| S-EPMC3601365 | biostudies-literature

miR-552 promotes ovarian cancer progression by regulating PTEN pathway.

Project description:BACKGROUND:Increasing researches have demonstrated the critical functions of MicroRNAs (miRNAs) in the progression of malignant tumors, including ovarian cancer. It was reported that miR-552 was an important oncogene in both breast cancer and colorectal cancer. However, the role of miR-552 in ovarian cancer (OC) remains to be elucidated. METHODS:RT-PCR and western blot analysis were used to detect the expression of miR-552 and PTEN. The impact of miR-552 on ovarian cancer proliferation and metastasis was investigated in vitro. The prognostic value of miR-552 was evaluated using the online bioinformatics tool Kaplan-Meier plotter. RESULTS:In the present study, we for first found that miR-552 was upregulated in ovarian cancer, especially in metastatic and recurrence ovarian cancer. Forced miR-552 expression promotes the growth and metastasis of ovarian cancer cells. Consistently, miR-552 interference inhibits the proliferation and metastasis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified Phosphatase and tension homolog (PTEN) as a direct target of miR-552. miR-552 downregulated the PTEN mRNA and protein expression in ovarian cancer cells. Furthermore, the PTEN siRNA abolishes the discrepancy of growth and metastasis capacity between miR-552 mimic ovarian cells and control cells. More importantly, upregulation of miR-552 predicts the poor prognosis of ovarian cancer patients. CONCLUSION:Our findings revealed that miR-552 could promote ovarian cancer cells progression by targeting PTEN signaling and might therefore be useful to predict patient prognosis.

| S-EPMC6900846 | biostudies-literature

Naringin promotes osteogenic differentiation of bone marrow stromal cells by up-regulating Foxc2 expression via the IHH signaling pathway.

Project description:Naringin is an active compound extracted from Rhizoma Drynariae, and studies have revealed that naringin can promote proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). In this study, we explored whether naringin could promote osteogenic differentiation of BMSCs by upregulating Foxc2 expression via the Indian hedgehog (IHH) signaling pathway. BMSCs were cultured in basal medium, basal medium with naringin, osteogenic induction medium, osteogenic induction medium with naringin and osteogenic induction medium with naringin in the presence of the IHH inhibitor cyclopamine (CPE). We examined cell proliferation by using a WST-8 assay, and differentiation by Alizarin Red S staining (for mineralization) and alkaline phosphatase (ALP) activity. In addition, we detected core-binding factor ?1 (Cbf?1), osteocalcin (OCN), bone sialoprotein (BSP), peroxisome proliferation-activated receptor gamma 2 (PPAR?2) and Foxc2 expression by using RT-PCR. We also determined Foxc2 and IHH protein levels by western blotting. Naringin increased the mineralization of BMSCs, as shown by Alizarin red S assays, and induced ALP activity. In addition, naringin significantly increased the mRNA levels of Foxc2, Cbf?1, OCN, and BSP, while decreasing PPAR?2 mRNA levels. Furthermore, the IHH inhibitor CPE inhibited the osteogenesis-potentiating effects of naringin. Naringin increased Foxc2 and stimulated the activation of IHH, as evidenced by increased expression of proteins that were inhibited by CPE. Our findings indicate that naringin promotes osteogenic differentiation of BMSCs by up-regulating Foxc2 expression via the IHH signaling pathway.

| S-EPMC5126353 | biostudies-literature

Notch3 promotes 3T3-L1 pre-adipocytes differentiation by up-regulating the expression of LARS to activate the mTOR pathway.

Project description:Adipocytes constitute a major component of the tumour microenvironment. Numerous studies have shown that adipocytes promote aggressiveness and invasion by stimulating cancer cells proliferation and modulating their metabolism. Herein, we reported that Notch3 promotes mouse 3T3-L1 pre-adipocytes differentiation by performing the integrative transcriptome and TMT-based proteomic analyses. The results revealed that aminoacyl-tRNA_biosynthesis pathway was significantly influenced with Nocth3 change during 3T3-L1 pre-adipocytes differentiation, and the expression of LARS in this pathway was positively correlated with Notch3. Published studies have shown that LARS is a sensor of leucine that regulates the mTOR pathway activity, and the latter involves in adipogenesis. We therefore supposed that Notch3 might promote 3T3-L1 pre-adipocytes differentiation by up-regulating LARS expression and activating mTOR pathway. CHIP and luciferase activity assay uncovered that Notch3 could transcriptionally regulate the expression of LARS gene. Oil Red staining identified a positive correlation between Notch3 expression and adipocytic differentiation. The activation of mTOR pathway caused by Notch3 overexpression could be attenuated by knocking down LARS expression. Altogether, our study revealed that Notch3 promotes adipocytic differentiation of 3T3-L1 pre-adipocytes cells by up-regulating LARS expression and activating the mTOR pathway, which might be an emerging target for obesity treatment.

| S-EPMC6933334 | biostudies-literature

NF-κB p65 promotes ovarian cancer cell proliferation and migration via regulating mortalin.

Project description:Previous studies show that mortalin, a HSP70 family member, contributes to the development and progression of ovarian cancer. However, details of the transcriptional regulation of mortalin remain unknown. We aimed to determine whether NF-κB p65 participates in the regulation of mortalin expression in ovarian cancer cells and to elucidate the underlying mechanism. Chromatin immunoprecipitation and luciferase reporter assay were used to identify mortalin gene sequences, to which NF-κB p65 binds. Results indicated that NF-κB p65 binds to the mortalin promoter at a site with the sequence 'CGGGGTTTCA'. Using lentiviral pLVX-NF-κB-puro and Lentivirus-delivered NF-κB short hairpin RNA (shRNA), we created ovarian cancer cell lines in which NF-κB p65 was stably up-regulated and down-regulated. Using these cells, we found that downregulation of NF-κB p65 inhibits the growth and migration of ovarian cancer cells. Further experimental evidence indicated that downregulation of NF-κB p65 reduced mortalin, and upregulation of mortalin rescued the proliferation and migration of ovarian cancer cells reduced by NF-κB p65 knockdown. In conclusion, NF-κB p65 binds to the mortalin promoter and promotes ovarian cancer cells proliferation and migration via regulating mortalin.

| S-EPMC6533498 | 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