Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393300 | ENA |
REPOSITORIES: ENA
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Project description:KRAS activation drives DNA methylation and silencing of specific tumor suppressor genes (TSGs). We previously showed that the ERK pathway induces transcriptional repression of TET1, which results in conversion of TSG promoters from a hydroxymethylated, active state to a hypermethylated and silenced state. Here we identified miR-29b as a KRAS-induced molecule that represses TET1 expression. In KRAS-transformed cells, ectopic miR-29b inhibition restores expression of TET1, thereby reactivating TSGs by reducing methylation and restoring hydroxymethylation. Mining gene expression data of lung cancer cell lines identified additional TSGs suppressed by KRAS signaling whose expression was restored by inhibition of miR-29b and re-expression of TET1. Because KRAS changes TSG promoters from hydroxymethylated to hypermethylated with miR-29b-dependent silencing of TET1, we demonstrate a model in which DNMT1 is present on target promoters prior to KRAS transformation. We also propose miR-29b as a potential circulating biomarker and target for rational treatment of specific malignancies.
2017-07-31 | GSE100857 | GEO
Project description:Overexpression and inhibition of miR-29 (pre-miR and anti-miR to miR-29b) in murine aortic smooth muscle cells, analysis of their secretome (conditioned media after serum starvation), n=3 for all four groups (pre-miR control, pre-miR-29b, anti-miR control, anti-miR-29b).
2016-05-06 | PXD003938 | Pride
Project description:Epigenetic silencing of the tumor suppressor RASSF4 favors multiple myeloma progression
| PRJNA335945 | ENA
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net ) : 165 lung adenocarcinomas without prior chemotherapy, hybridized on Illumina SNP HumanCNV370 and Affymetrix HGU133Plus2 arrays. Project leader : Prof. Pierre FOURET (pierre.fouret@igr.fr). Note: Bronchiolo-alveolarComponent : a non invasive tumor component shown in well differentiated tumor cells. EGFR Gene Mutation Status: Gene mutation status of epidermal growth factor receptor (erythroblastic leukemia viral (v; -erb-b) ; oncogene homolog, avian) ; HGNC:3236 ; Approved Symbol:EGFR; Chromosome:7p12 ; UniProt ; ID:P00533 ; OMIMID:131550 ; EntrezGeneID:1956 ; ; RefSeq:NM_201283 ; M=mutated ; WT=non mutated=wild type. KRAS Gene Mutation Status: Gene mutation status of v-Ki-ras2 Kirsten rat ; sarcoma viral oncogene homolog ; HGNC:6407 ; Approved Symbol:KRAS ; Chromosome:12p12.1 ; UniProtID:P01116; OMIM ID:190070 ; EntrezGeneID:3845 ; ;RefSeq:NM_033360 ; M=yes=mutated ; WT=non mutated.
2012-10-19 | E-MTAB-923 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:miR-30-5p functions as a tumor suppressor by targeting BCL9
| PRJNA217455 | ENA
Project description:Transcriptomic profiling of HeLa cells treated with miR-29b-2-5p and control-miR
| PRJNA305265 | ENA
Project description:KRAS mutation is one of the major genetic alterations in colorectal cancer (CRC). Treating patients with KRAS mutant CRC remains one of the biggest challenges in oncology. In this study, we aimed to discover an effective therapeutic microRNA (miRNA) that could target KRAS mutant CRC. For this purpose, we investigated the functional relevance of dysregulated miRNAs in KRAS mutant cancers. We transfected exogenous KRASG12V into human embryonic kidney 293 (HEK293) cells and human lung fibroblasts (MRC5) cells, and performed comprehensive microRNA expression profiling by microarray analysis. The results showed that 6 miRNAs are significantly upregulated in KRAS-transfected HEK293 and MRC5 cells. Among 6 miRNAs, we identified mature miRNA-29b-1-5p as potent growth inhibitor in CRC cell proliferation. However, miRNA-29b-1-5p was found to be a passenger strand with a star form (miRNA-29b-1-5p*), and did not function in CRC cells. Proliferation assay revealed that completely opposite complementary strand to miRNA-29b-1-5p possessed a potent anti-tumor effect. We named this novel anti-tumor siRNA sequence “MIRTX”. MIRTX induced apoptosis and significantly inhibited cell proliferation in KRAS mutant CRC in vitro. In addition, MIRTX suppressed NF-κB signaling pathway, which is downstream effector of KRAS in CRC. Furthermore, MIRTX directly targeted 3'-UTR of PIK3R1 and CXCR2 mRNA, and indirectly suppressed KRAS itself. In vivo xenograft mouse models, systemic administration of MIRTX significantly inhibited the tumor growth with no particular toxicity, using carbonate apatite as a vehicle. These findings indicate that inhibition of NF-κB signaling by siRNA-based therapeutic could be a promising strategy against KRAS mutant CRC.
2018-03-17 | GSE83634 | GEO
Project description:Ras family oncogenes are mutated in approximately 30% of human cancers and cause resistance to multiple treatment modalities. While identifying methods to directly target mutant KRas have been challenging, targeting regulators of KRas may be beneficial. Using a systems approach of integrating a genome-wide miRNA screen with patient data of a phospho-proteomic signature of the KRas downstream pathway, we identified miR-193a-3p as a potent tumor suppressor capable of reversing KRas-related signaling, whereby the 3’UTR of KRas is directly targeted via two miR-193a-3p binding sites. Mechanistic studies revealed that miR-193a-3p inhibited the KRas protein signature, KRas downstream transcriptomic network, proliferation, induced a G1 arrest, and reduced colony formation in 3D cultures through direct targeting of KRas. An ex vivo lung cancer model showed that miR-193a-3p significantly reduced the viability of circulating tumor cells as well as decreased metastasis. In vivo studies revealed that miR-193a-3p significantly reduced tumor growth as well as metastasis of a KRas-mutant lung cancer xenograft model.
2016-09-18 | GSE73194 | GEO