P53 regulated microRNAs in the presence/absence of caesin kinase 1 alpha (CK1alpha)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94908 | GEO | 2017/02/16
SECONDARY ACCESSION(S): PRJNA374789
REPOSITORIES: GEO
Similar Datasets
Project description:Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.
| EGAS00001006678 | EGA
Project description:MicroRNAs (miRNAs) are intrinsic regulators in the various cellular processes, and their abnormalities are considered to be involved in the onset of human disorders, including cancer. Circulating miRNA is focused as new cancer biomarker however it is regarded that circulating RNA are released not only from tumor but also by various pathways. Recently, exosomes, small membrane vesicles, have been a major interest in cancer research field, because of their unique biological properties. Exosomes are secreted from various cells and the components (Lipids, mRNAs, miRNAs and proteins) reflect origin of the cells secreting them. Identification of exosomal miRNAs from cancer cells is expected to provide useful biomarkers of cancer. To identify specific exosomal miRNAs as candidate biomarkers for colorectal cancer, we compared exosomal miRNA profiles of 5 colon cancer cell lines with that of normal colon-derived epithelial cells, and isolated a subset of miRNAs as commonly-secreted miRNAs from colon cancer cells Endogenously expression of microRNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) using total RNA of three human colon cancer cell lines (HT-29 cells, SW48 cells, and RKO cells) at two independent experiments. Exosomal microRNAs were analyzed by microRNA microarray using total RNA of exosomes from conditioned media of three human colon cancer cell lines, HT-29 cells, SW48 cells, and RKO cells at three independent experiments. Exosomes were prepared by step-wise ultra-centrifugation methods. RNA was prepared by Trizol or Trizol-LS reagent (Invitrogen) and RNeasy mini spin column (Qiagen).
2014-04-01 | E-GEOD-39832 | biostudies-arrayexpress
Project description:Gene expression profiles of methylated or nonmethylated miRNA oligonucleotides transfected DICER exon 5-disrupted RKO cells.
2017-07-01 | GSE75927 | GEO
Project description:Blood is a rich source of proteins for mosquitoes, but also contains many other molecules such as microRNAs (miRNAs). Here, we found that human blood miRNAs are transported in abundance into the fat body tissue of Aedes aegypti, a key metabolic center in post-blood feeding reproductive events, where they target and regulate mosquito genes.
2021-06-28 | PXD023190 | Pride
Project description:Gene expression profiles of methylated or nonmethylated miRNA oligonucleotides transfected DICER exon 5-disrupted RKO cells.
2017-07-01 | GSE83740 | GEO
Project description:Patients with advanced colorectal cancer (CRC) are commonly treated with systemic combination therapy but suffer eventually from drug resistance. MicroRNAs (miRNAs) are suggested to play a role in treatment resistance of CRC. We studied whether restoring downregulated miR-195-5p and 497-5p sensitize CRC cells to currently used chemotherapeutics 5-fluorouracil, oxaliplatin and irinotecan. Sensitivity to 5-FU, oxaliplatin and irinotecan before and after transfection with miR-195-5p and miR-497-5p mimics was analyzed in CRC cell lines HCT116, RKO, DLD-1 and SW480. Mass spectrometry based proteomic analysis of transfected and wild-type cells was used to identify targets involved in sensitivity to chemotherapy. Proteomic analysis revealed 181 proteins with significantly altered expression after transfection with miR-195-5p mimic in HCT116 and RKO, including 118 downregulated and 63 upregulated proteins. After transfection with miR-497-5p mimic, 130 proteins were significantly downregulated and 102 were upregulated in HCT116 and RKO (P<0.05 and FC<-3 or FC>3). CHUK and LUZP1 were coinciding downregulated proteins in sensitized CRC cells after transfection with either mimic. Resistance mechanisms of these two proteins may be related to nuclear factor kappa-B signaling and G1 cell cycle arrest, respectively. Restoring miR-195-5p and miR-497-5p expression enhanced sensitivity to chemotherapy, mainly oxaliplatin, in CRC cells and could be a promising treatment strategy for patients with mCRC. Proteomics revealed potential targets of these miRNAs involved in sensitivity to chemotherapy.
2019-09-27 | PXD015369 | Pride
Project description:Question Addressed: What is the host response (specifically apoptosis pathways) to Shigella infection and what is the contribution of MxiE to the host response? The arrays are apoptosis Exon hit arrays, thus splice variation can be determined. Array data from HeLa cells that remained Uninfected or were infected with wildtype S. flexneri serotype 2a strain 2457T or an isogenic mixE mutant. These groupings are further divided such that Uninfected or Infected cells remained untreated or were treated with the apopotosis inducer staurosporine (STS). The design of the experiment was a time course and samples were harvested at the indicated time points (hr). All hybridizations were conducted against a common reference sample that was made from pooled samples of normal uninfected healthy HeLa cells. Infection: HeLa cells were infected with wt Shigella (wt), mxiE mutant (mixE) or were left uninfected (uninfected) Compound Based Treatment: Cultures were treated with Staurosporin (STS) or were left untreated (untreated) Infection time: Cells were harvested at the indicated time after treatment
2013-05-21 | GSE38086 | GEO
Project description:Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in a variety of tumor types, most notably in Anaplastic Large Cell Lymphoma (ALCL) where a chromosomal translocation generates the oncogenic fusion protein, Nucleophosmin-ALK (NPM-ALK). Whilst much is known regarding the mechanism of transformation by NPM-ALK, the existence of cellular defence pathways to prevent this pathological process has not been investigated. Employing the highly tractable primary murine embryonic fibroblast (MEF) system we show that cellular transformation is not an inevitable consequence of NPM-ALK activity but is combated by p53 and Rb. Activation of p53 and/or Rb by NPM-ALK triggers a potent proliferative block with features reminiscent of senescence. While loss of p53 alone is sufficient to circumvent NPM-ALK-induced senescence and permit cellular transformation, sole loss of Rb permits continued proliferation but not transformation due to p53-imposed restraints. Furthermore, NPM-ALK attenuates p53 activity in an Rb and MDM2 dependent manner but this activity is not sufficient to bypass senescence. These data indicate that senescence may constitute an effective barrier to ALK-induced malignancies that ultimately must be overcome for tumor development.
| S-EPMC3056788 | biostudies-literature
Project description:Here, we report 2 novel intron gains segregating in populations of Daphnia pulex endemic to Oregon. These novel introns do not have an obvious source and are not present in any D. pulex populations outside Oregon, other species of Daphnia that we examined, or any other organism for which sequence data are available. Furthermore, the novel introns are both found in the same gene, a Rab GTPase (rab4), and they appear to differ in their insertion site by one base pair, providing some support to the proto-splice site hypothesis. The rarity of intron-gain polymorphisms is questioned as we discovered 2 events in an initial survey of only 6 nuclear loci in 36 Daphnia individuals. Neutrality tests failed to ascertain a clear selective effect for either intron insertion, and a significant difference in recombination rate was not observed in alleles that contain the novel intron insertion versus alleles lacking it. We conclude that one novel intron insertion segregating at high frequencies in Daphnia populations in Oregon is unlikely to be adaptive and may result from the reduced efficacy of selection in isolated populations of small effective size.
| S-EPMC2727387 | biostudies-literature
Project description:The human glioma cell line M059J is deficient in DNA-dependent protein kinase (DNA-PK) due to a frame-shift mutation in PRKDC, the gene for its catalytic subunit, while cell line M059K, isolated from the same malignant tumor, has normal DNA-PK activity. DNA-PK is required for double-strand DNA break repair, and its absence is responsible for increased radiosensitivity of M059J. We show that transcripts of several melanoma antigen subfamily A (MAGE-A) genes, the expression of which is restricted to tumor and germ-line cells,are present in M059K, but that their expression is strongly downregulated in M059J. Normal levels of MAGE-A expression are restored in the PRKDC-complemented cell line M059J/Fus1, suggesting that the presence of DNA-PK is required for MAGE-A gene transcription. We also show that the MAGE-A1 promoter is methylated in M059J, while the promoter is demethylated in M059K and M059J/Fus1. Other genes, including all three major histocompatibility class I (HLA) genes, BENE, and an unnamed gene related to CNIL(CORNICHON-like), display an opposite expression profile (i.e., they are upregulated in the DNA-PK-deficient cell line, but show low levels of expression in both M059K and in the PRKDC-complemented cell line). For these genes, differential expression does not correlate with DNA methylation in upstream promoter sequences. Our results suggest that the presence of DNA-PK can exert effects on gene expression by various mechanisms and pathways, thus affecting overall cell physiology even in the absence of DNA damage.
| S-EPMC5991153 | biostudies-literature