Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antitumor efficacy of sequence specific DNA-targeted gamma PNA based cMyc inhibitor

ABSTRACT: Targeting oncogenes at the genomic DNA level can open new avenues for precision medicine. Significant efforts are ongoing to target oncogenes using diverse RNA-targeted and protein-targeted platforms, but no progress has been made to target genomic DNA for cancer therapy. Here, we introduce a gamma peptide nucleic acid (PNA)-based genomic DNA-targeted platform to silence oncogenes in vivo. gPNAs can efficiently invade the mixed sequences of genomic DNA with high affinity and specificity. As a proof-of-concept, we established that gPNA could inhibit c-Myc transcription in multiple cell lines. In vivo efficacy and safety of the DNA-targeted approach were demonstrated in three pre-clinical models. We also established that anti-transcription gPNA in combination with histone deacetylase inhibitors (HDACi) and chemotherapeutic drugs results in high and robust antitumor activity in cell-line and patient-derived xenografts. Overall, this strategy offers a unique therapeutic platform to target genomic DNA to inhibit oncogenes for cancer therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246439 | GEO | 2023/11/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Antitumor efficacy of sequence specific DNA-targeted gamma PNA based cMyc inhibitor

Project description:Antitumor efficacy of sequence specific DNA-targeted gamma PNA based cMyc inhibitor

| PRJNA1032932 | ENA

Transcriptome analysis of Leishmania infantum PNA+ and PNA- promastigotes by complete shotgun DNA microarrays

Project description:Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis in Mediterranean areas and also acts as an opportunistic parasite in HIV patients. Metacyclic promastigotes are transmitted during bloodmeals of the sand-fly host after development. Metacyclogenesis can be micmiked in axenic cultures and peanut lectin (PNA) agglutination followed by two-step centrifugation allows the separation of procyclic and metacyclic promastigotes in L. major. The purpose of this study is to isolate both fractions simultaneously from the same population of L. infantum in stationary phase of axenic culture and compare their expression profiles through DNA microarrays, specially focusing on metacyclic promastigotes. Whole-genome shotgun DNA microarrays were constructed and used to analyse the stationary-phase procyclic and metacyclic expression profiles. Four biological replicates of the experiment were performed and analysed, so that 322 clones with meaningful values of stage-specific regulation were selected. We found several genes dealing with primary metabolism, differentiation in procyclic promastigotes and with development of infectivity in metacyclic promastigotes. The differences we have found between the procyclic (PNA+) and metacyclic (PNA-) transcriptomes demonstrate that negative selection of metacyclic promastigotes through PNA agglutination is suitable in L. infantum and both fractions can be isolated. In addition, up-regulation of genes implied in lipophosphoglycan (LPG), proteophosphoglycan (PPG) and glycoprotein biosynthesis indicate that metacyclic promastigotes are related with infectivity. Keywords: comparative hybridization between cDNAs from procyclic PNA+ and metacyclic PNA- promastigotes of L.infantum

2009-05-14 | GSE11269 | GEO

Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli

Project description:Antisense peptide nucleic acids (PNAs) that target mRNAs of essential bacterial genes exhibit specific bactericidal effects in several microbial species, but our mechanistic understanding of PNA activity and their target gene spectrum is limited. Here, we present a systematic analysis of PNAs targeting eleven essential genes with varying expression levels in uropathogenic Escherichia coli (UPEC). We demonstrate that UPEC is susceptible to killing by peptide-conjugated PNAs, especially when targeting the widely-used essential gene acpP. Our evaluation yields three additional promising target mRNAs for effective growth inhibition, i.e., dnaB, ftsZ, and rpsH. The analysis also shows that transcript abundance does not predict target vulnerability and that PNA-mediated growth inhibition is not universally associated with target mRNA depletion. Global transcriptomic analyses further reveal PNA sequence-dependent but also -independent responses, including the induction of envelope stress response pathways. Importantly, we show that the growth inhibitory capacity of 9mer PNAs is generally as effective as their 10mer counterparts. Overall, our systematic comparison of a range of PNAs targeting mRNAs of different essential genes in UPEC suggests important features for PNA design, reveals a general bacterial response to PNA conjugates and establishes the feasibility of using PNA antibacterials to combat UPEC.

2022-04-28 | GSE191313 | GEO

Regulatory RNA inhibition in human phagocytes using cell-penetrating PNA oligonucleotides

Project description:Here, we determined the ability of peptide nucleic acid (PNA) oligomers, coupled to different cell-penetrating peptides (CPPs), to interfere in regulatory RNA circuits of human blood-derived leukocytes. Using RNA-seq, FACS and confocal microscopy we identified octaarginin as a CPP enabling PNA delivery and sequence-dependent RNA inhibition in blood-derived myeloid cells at nanomolar concentration. At 200 nM, an R8-PNA targeting immune-regulatory microRNA-155 was delivered into nearly 100 % of human macrophages within 24 hours without apparent cytotoxicity, and globally de-repressed microRNA-155 target-mRNAs. This was not observed when coupling the PNA inhibitor to a K3 instead of the R8 peptide. We suggest that CPP choice is a fundamental success-determining factor for therapeutic RNA-inhibition in human myeloid leukocytes.

2021-03-01 | GSE152740 | GEO

miRNA-seq in ovarian tissues of prenatally androgenized (PNA) mice

Project description:To investigate the molecular mechanisms of miRNA-mRNA expression underlying this phenotype, ovarian samples from PNA and control mice were subjected to microRNA-seq and RNA-seq. Differential expression analyses were carried out to identify differentially expressed microRNAs (DEmiRs) and differentially expressed genes (DEGs). Target genes of DEmiRs were predicted by miRTarbase and visualization by Cytoscape. Functional annotation and pathway enrichment analyses for the DEGs and target genes were performed through the DAVID database. Then, to reveal the interactions involved in the pathogenesis of PCOS, the integrated analysis of miRNA-mRNA was performed in PNA mice vs. controls and granulosa cells (GCs) of PCOS women vs. health women. Protein–protein interaction (PPI) networks were established for these negatively regulated pairs via the STRING database. The expression and correlation of potential miRNAs and targets were further validated using RT-qPCR in more PNA mice and clinical human granulosa cells.

2021-03-04 | GSE168166 | GEO

MBD-seq in ovarian tissues of prenatally androgenized (PNA) mice

Project description:To investigate the molecular mechanism of PCOS underlying the hyperandrogenic phenotype, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Methylated DNA binding domain sequencing (MBD-seq) and RNA-seq were performed on PNA mice (n=6) and control group (n=4) and validations were applied on ovarian samples from PNA mice (n=6) and control group (n=6) using MSP (methylation-specific PCR) and qPCR. The immunohistochemistry (IHC) and transmission electron microscope (TEM) profiling was separately conducted on tissue sections and granular cells of PNA mice (n=6) and control group (n=6). We identified 857 genes with differently methylated promoters and 3317 differently expressed genes in PNA mice and control group. We found that PCOS group had a down-regulation of Dnmt1 gene expression, accompanied by global hypomethylation compared with the control group. The promoter regions of Map3k1(mitogen-activated protein kinase kinase kinase 1) and Map1lc3ka (microtubule-associated protein1 light chain 3) were hypomethylated, accompanied by up-regulation of their mRNA expression, which may be involved in the regulation of PCOS through MAPK/p53 pathway activition and autophagy alteration.

2020-08-28 | GSE156960 | GEO

RNA-seq in ovarian tissues of prenatally androgenized (PNA) mice

2020-08-28 | GSE156895 | GEO

Ovaries of PNA mice and controls

Project description:To investigate the etiology of the hyperandrogenic phenotype of polycystic ovary syndrome (PCOS), a prenatally androgenized (PNA) mouse model was validated and used for microarray analysis.

2017-11-01 | GSE103056 | GEO

Inhibition of MYCN by a PNA anti-gene in alveolar rhabdomyosarcoma

Project description:The objective was to identify the molecular mechanisms responsible for in vitro and in vivo efficacy of an anti-MYCN peptide nucleic acid on a preclinical model of alveolar rhabdomyosarcoma. Cells treated with a anti-MYCN PNA exhibit growth arrest and apoptosis, and in vivo tumor growth is blocked. Keywords: oncogene inhibition RH30 alveolar rhabdomyosarcoma cell line was treated with a 10uM concentration of anti-MYCN PNA or a mutated PNA devoid of any activity. After 12 hours RNA was extracted from untreated and treated cells and gene expression was analyzed by Affymetrix Gene Chips.

2011-12-31 | E-GEOD-7959 | biostudies-arrayexpress

full scale PNA

Project description:full scale PNA Raw sequence reads

| PRJNA917425 | ENA