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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profile of STAT3 in ovarian cancer cell (SKOV3ip1)

ABSTRACT: RNA interference (RNAi) holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of siRNA. To achieve this goal, we have established a novel formulation of siRNA by incorporating it into reconstituted high density lipoprotein (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the scavenger receptor type B1 (SR-B1). Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in targeting either signal transducer and activator of transcription 3 (STAT3) or focal adhesion kinase (FAK) expression in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore this novel technology could serve as the foundation for new cancer therapeutic approaches. To identify the role of STAT3 in ovarian cancer cell, we performed microarray after knocking down STAT3 in ovarican cancer cells (3 siCon and 3 siSTAT3).

ORGANISM(S): Homo sapiens

SUBMITTER: Sangbae Kim

PROVIDER: E-GEOD-20597 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profile of STAT3 in ovarian cancer cell (SKOV3ip1)

Project description:RNA interference (RNAi) holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of siRNA. To achieve this goal, we have established a novel formulation of siRNA by incorporating it into reconstituted high density lipoprotein (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the scavenger receptor type B1 (SR-B1). Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in targeting either signal transducer and activator of transcription 3 (STAT3) or focal adhesion kinase (FAK) expression in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore this novel technology could serve as the foundation for new cancer therapeutic approaches.

2011-12-22 | GSE20597 | GEO

STAT3-mediated CD133 upregulation promotes hepatocellular carcinoma

Project description:We identified a novel mechanism by which IL-6/STAT3 signaling up-regulates CD133 expression and promotes HCC progression. STAT3 activation upregulates the expression of CD133 during liver carcinogenesis. Targeting STAT3-mediated CD133 overexpression may represent a promising therapeutic strategy for HCC patients via eradicating the liver tumor microenviornment. To develop novel cancer therapeutic strategies by identification of signaling pathways or biomarkers and understanding their functions on cancer stem cell biology, we determined CD133 expression and STAT3 activation with tumor microenvironment in HCC patient tissues. The relation of STAT3 activation and CD133 expression was investigated by luciferase assay, shRNA knock-down, and chromatin immunoprecipitation assay in HCC cells, and in vivo xenograft model.

2014-08-08 | E-GEOD-60194 | biostudies-arrayexpress

Design of a novel highly efficient peptide-based siRNA-delivery vector, PepFect6

Project description:While small interfering RNAs (siRNAs) have been rapidly appreciated to induce gene silencing, efficient vectors for primary cells and for systemic in vivo delivery are lacking. We here present a novel chemically modified cell-penetrating peptide named PepFect6 (PF6) for efficient delivery of siRNAs into various types of cells including e.g. lymphocyte suspension cells and primary embryonic stem cells. Stable PF6/siRNA nano- particles rapidly enter entire cell populations resulting in strong and persistent RNAi responses, without associated transcriptomic or proteomic changes. In contrast to the majority of chemical reagents, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by the presence of serum. Finally, strong RNAi responses are observed in two different in vivo models following systemic delivery of PF6/siRNA in mice. Taken together, PF6 is an efficient siRNA delivery vector with superior delivery properties as compared to other tested transfection reagents.

2009-12-31 | GSE19702 | GEO

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [CUT&RUN]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Epegnomic profiling was performing on cells lines after lipid nanoparticles in vitro.

2022-11-09 | GSE217110 | GEO

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [ATAC-seq]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Chromatin Accessibility (ATAC-seq) was performing on cells lines after lipid nanoparticles in vitro.

2022-11-09 | GSE217112 | GEO

BV-2 cells treated with different nanoparticles

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2023-10-01 | PXD044395 | Pride

Therapeutic Delivery of Targeted Nanoparticle Cannabinoid Equivalents

Project description:Nanoparticles and nano delivery systems are continuously being refined and developed as means of treating numerous human diseases by site-specific, and target-oriented delivery of medicines. The nanoparticles can carry therapeutic cargo or be medicinal themselves by virtue of their constitutional structural components. Here we report the ability of synthetic N-acylethanolamides, linoleoylethanolamide (LEA) and oleoylethanolamide (OEA), with endocannabinoid-like activity, to form spherical colloidal nanoparticles that when conjugated with tissue specific homing molecules, can localise to specific areas of the body, and reduce inflammation. The opportunities to mediate pharmacological effects of endocannabinoids at targeted sites provides a novel drug delivery system with increased medicinal potential to treat many diseases in many areas of medicine.

2022-10-19 | GSE206164 | GEO

Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in t(8;21)-positive Acute Myeloid Leukemia [RNA-seq]

Project description:To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA. Gene expression profiling was performing on cells lines after lipid nanoparticles in vitro and on harvested cells from treated mice in vivo.

2022-11-09 | GSE217109 | GEO

Homo sapiens

Project description:Design of a novel highly efficient peptide-based siRNA-delivery vector, PepFect6

| PRJNA121883 | ENA

MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (microRNA signatures retrieved from rHDL injected into WT, ApoE-/- chow, ApoE-/-high fat diet)

Project description:Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs. microRNA signatures retrieved from rHDL injected into WT, ApoE-/- chow, ApoE-/-high fat diet Profiled rHDL miRNA signatures from n=3 WT; n=3 ApoE-/- chow, n=4 ApoE-/- high fat mice

2011-03-23 | E-GEOD-25424 | biostudies-arrayexpress

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