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MicroRNA-431 promotes metastasis of pancreatic neuroendocrine tumors by targeting DAB2IP, a RasGAP tumor suppressor

ABSTRACT: MicroRNA-431 promotes metastasis of pancreatic neuroendocrine tumors by targeting DAB2IP, a RasGAP tumor suppressor

PROVIDER: PRJNA578481 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10313828_1.fastq.gz	Fastqsanger.gz
	SRR10313828_2.fastq.gz	Fastqsanger.gz
	SRR10313829_1.fastq.gz	Fastqsanger.gz
	SRR10313829_2.fastq.gz	Fastqsanger.gz
	SRR10313830_1.fastq.gz	Fastqsanger.gz

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MicroRNA-431 promotes metastasis of pancreatic neuroendocrine tumors by targeting DAB2IP, a RasGAP tumor suppressor

Project description:Analysis of pathways regulated by miR-431 at the mRNA expression levels in pancreatic neuroendocrine tumor cells

2019-11-21 | GSE139119 | GEO

GSF1635: RNA-seq data of OVCAR3-DAB2IP expressing cells vs. control

Project description:Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies in the US. Ovarian cancer stem cells (OCSCs) have been shown to drive chemoresistance and tumor progression but the mechanism remains incompletely understood. Disabled Homolog 2- Interacting Protein (DAB2IP) is a potent tumor suppressor identified in multiple types of cancers and we demonstrate that DAB2IP is silenced by the repressive epigenetic mark H3K27me3 at the DAB2IP promoter loci in OCSCs.

2020-09-30 | GSE144948 | GEO

Effects of DAB2IP expression on gene expression in DLD1 cells

Project description:To assess the function of DAB2IP in colon cancer, we expressed DAB2IP or control LACZ in DLD1 cells which lack DAB2IP.

2023-03-05 | GSE224869 | GEO

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DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

Project description:Despite proven therapy options for estrogen receptor (ER)-positive tumors, a significant number of patients with these cancers exhibit relapse with associated metastasis. Studies have shown that the loss of expression of RasGAPs leads to aggressive phenotypes and poor outcomes in several cancers including breast cancer. In our study, mining TCGA gene expression profiles of ER-positive breast tumors, we found that low expression of the RasGAP, DAB2IP is associated with a significant decrease in relapse-free survival in patients with Luminal A breast tumors. Immunostaining found that DAB2IP loss occurs in grade 2 tumors and higher. Consistent with this, genes upregulated in low DAB2IP Luminal A tumors are shared with more aggressive tumor subtypes, and are associated with proliferation, metastasis, and enhanced ER-signaling. In addition, cell-based studies reveal that low DAB2IP expression in ER-positive breast cancer cells is associated with increased proliferation, enhanced stemness phenotypes, and activation of IKK, the upstream regulator of the NF-B signaling pathway. Further, integrating cell-based ChIP-seq with motif analysis and TCGA RNA-seq data, we identify a candidate set of NF-B target genes that are upregulated with loss of DAB2IP and are proposed to regulate several oncogenic phenotypes, including altered RNA processing. This study provides new insight into mechanisms associated with aggressiveness and recurrence within a subset of Luminal A breast cancers that are otherwise typically less aggressive. Gene expression profiling by RNA-sequencing of DAB2IP knockdown and control MCF10A cells.

2024-12-18 | GSE227876 | GEO

DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

2024-12-18 | GSE227875 | GEO

RHAMMB promotes metastasis of pancreatic neuroendocrine tumor

Project description:Analysis of molecular mechanisms by which RHAMMB promote metastasis of pancreatic neuroendocrine tumor.

2024-04-16 | GSE200497 | GEO

Effects of DAB2IP depletion on gene expression in HCT116 cells

Project description:To study DAB2IP function on colon cancer, we depleted DAB2IP in HCT116 cells using shDAB2IP or shCNT(scramble) as a control.

2023-03-05 | GSE224870 | GEO

RHAMMB promotes metastasis of pancreatic neuroendocrine tumor

Project description:RHAMMB promotes metastasis of pancreatic neuroendocrine tumor

| PRJNA824826 | ENA

miR-431 Promotes Metastasis of Pancreatic Neuroendocrine Tumors by Targeting DAB2 Interacting Protein, a Ras GTPase Activating Protein Tumor Suppressor.

Project description:The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. A better understanding of the drivers of PNET tumorigenesis is urgently needed. Distinct miRNA signatures have been identified for different stages of tumorigenesis in both human and mouse PNETs. The functions of these miRNAs are poorly understood. miR-431 is the most up-regulated miRNA in the metastatic signature. However, it is unknown whether miR-431 contributes to metastasis of PNETs. Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro, and metastasis in both xenograft and spontaneous mouse models of PNET. Treatment of PNET cells with Erk inhibitor or locked nucleic acids sequestering miR-431 inhibits invasion. Four target prediction modules and dual-luciferase reporter assays were used to identify potential mRNA targets of miR-431. A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 target. Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. Taken together, miR-431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. miR-431 may be targeted to manage metastatic PNETs.

| S-EPMC7074368 | biostudies-literature

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