Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival

ABSTRACT: Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide Unique mutational combinations can result in distinct changes to gene regulatory mechanisms leading to variability in the efficacy of available therapeutics. To work toward novel therapeutic strategies, it is important to understand the mechanisms by which unique combinations of mutations affect gene regulatory mechanisms. To that end, in this study, we generated RNA- and small RNA-seq data from Apc (A; n=3), Apc/Kras/p53 (AKP; n=1), B-catenin (B; n=5), B-catenin/Kras/p53 (BKP; n=1), Kras/Rspo3/p53 (KRP; n=2), Kras/Rspo3/p53/Smad4 (KRPS; n=4), Kras/Rspo3/Smad4 (KRS; n=3), Rspo3 (R; n=2) mutant mouse enteroids, and wild-type (WT; n=2) controls. From this analysis, we found that miR-24-3p is upregulated master miRNA regulator across mutational contexts. Functional studies identified miR-24-3p as a regulator of cell survival. Utilizing RNA- and leChRO-seq from HCT116 cells treated with a miR-24-3p inhibitor (n=3) or scramble control (n=3), we identified HMOX1 and PRSS8 as candidate miR-24-3p targets subject to post-transcriptional regulation by miR-24-3p.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE188212 | GEO | 2022/11/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional Profiling of Mouse Tumours

Project description:Murine small intestinal and colonic tumours with mutations in combinations of Kras, P53, Notch1, Apc and Braf.

2023-04-05 | GSE218776 | GEO

GEMM CRC collection analysis

Project description:A collection of genetically engineered mouse models (GEMM) of colorectal cancer (CRC) were created, and primary tumors from these GEMMs were analyzed. Primary CRC tumors from these GEMMs were genotyped to confirm that they contain the core genetic lesions of interest, including APC, P53, KRAS, and BRAF. Primary tumors from GEMMs with combinations of lesions of interest were analyzed by whole genome expression, and their expression profiles were compared to determine how they segregate. Signatures were then generated from GEMM tumors of interest and compared to human clinical datasets with expression and outcome data. Primary tumors from CRC GEMMs with different combinations of mutant alleles of interested were generated and analyzed. Alleles include mutant forms of APC (A), P53 (P), KRAS (K) and BRAF (B).

2014-07-01 | E-GEOD-50794 | biostudies-arrayexpress

miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells

Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.

2017-03-29 | MSV000080762 | MassIVE

Molecular Mechanisms Associated with Primary Open-angle Glaucoma with MicroRNA Microarray Data

Project description:This study aimed to investigate the molecular mechanism responsible for primary open-angle glaucoma (POAG) progression. We analyzed microRNAs (miRNAs) expression profiling in aqueous humor (AH) of both POAG patients and normal controls, using a microarray-based approach. Subsequently, differentially expressed miRNAs (DEmiRNAs) were identified using Bayes moderated t-test. Next, DEmiRNAs target genes were predicted based on miRNA databases, followed by GO analysis and pathway analysis using DAVID. Furthermore, OAG-related genes analysis for target genes was carried out using CTD database, respectively. Finally, verification of DEmiRNAs expression levels was performed by RT-qPCR. A total of 40 significant DEmiRNAs were identified between control and POAG groups, including 24 up-regulated miRNAs and 16 down-regulated miRNAs. Further, the target genes of hsa-miR-206, including BMP2, SMAD4, ID2, and TNF, were mainly enriched in transforming growth factor-β (TGF-β) signaling pathway. While, target genes of hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p, including BCL2, EPHB2, VEGFA, COL4A1, APC, and TGFBR1, were enriched in eye development. Moreover, FNDC3B, CAV2 and VEGF, target genes of hsa-miR-206 or hsa-miR-34c-5p, were the OAG-related genes. Ultimately, RT-qPCR analysis confirmed that mRNA levels of hsa-miR-206, hsa-miR-7-2-3p, and hsa-miR-20b-3p were increased, while those of hsa-miR-184 and hsa-miR-34c-5p were decreased in POAG compared with normal groups (P < 0.05). Hsa-miR-206, hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p might play a significant role in the pathogenesis of POAG and hsa-miR-206 might be associated with the development of POAG by regulating TGF-β signaling pathway. These results might provide insight toward a better understanding of the pathogenesis of POAG.

2015-08-04 | GSE71639 | GEO

Multi-omic study of genome-edited human colonoids reveal patterns of microRNA regulation specific to different colorectal cancer mutation profiles

Project description:Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide Unique combinations of mutations can affect responsiveness to specific therapeutics. This can be, at least in part, due to mutation-specific alterations in gene regulatory mechanisms. To better understand how unique combinations of mutations affect gene regulation, we generated small RNA-seq, length extension chromatin run-on-seq (leChRO-seq), and RNA-seq data from APC (A-mutant), APC/KRAS (AK-mutant), APC/KRAS/TP53 mutant (AKP-mutant), and iGFP control human colonic organoids. From these analyses, we found that our colonic organoid models demonstrate mutation-specific patterns of miRNA transcription, miRNA expression and transcriptional regulatory element actvitiy. Furthermore, we defined 10 patterns of miRNA expression across organoid models. We highlighted one group of miRNAs that exhibited a unique downregulation of expression in AKP-mutant organoids (including miR-34a-5p and miR-10a-5p). Analysis of miRNA transcription revealed that most changes in miRNA expression are correlated with changes in miRNA transcription. Analysis of leChRO-seq data revealed that transcriptional regulatory elements upregulated in AKP-mutant colonic organoids have an enrichment of predicted binding sites for oncogenic transcription factors.

2023-12-31 | GSE231436 | GEO

Expression data from genetically engineered mouse models (GEMMs)

2013-07-02 | GSE39557 | GEO

KRas targeting by clinically significant miR-193a-3p inhibits mutant KRas lung cancer growth, circulating tumor cells and metastasis in vivo

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

Expression data from genetically engineered mouse models (GEMMs)

Project description:3 Cell lines from Apc, p53 (AP) GEMMs were compared to 12 cell lines from Apc, Kras, p53 (AKP) GEMMs. Mouse 430 2.0 arrays were used to determine genomic expression differences between the two genotypes (AP and AKP). RNA was extracted from 3 AP and 10 AKP cell lines using the Qiagen RNEasy kit, and hybridized to individual Affymetrix mouse 430 2.0 chips as per manufacturer's instructions

2013-07-02 | E-GEOD-39557 | biostudies-arrayexpress

Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer (bulk RNA-seq)

Project description:We utilized bulk RNA sequencing to assess intrinsic differences between wildtype and autophagy-defective (Atg16l1 deleted) AKPS colorectal cancer organoids in both untreated and IFN gamma treated conditions. AKPS mutations consist of loss-of-function in tumor suppressors Apc, Trp53, Smad4, and gain-of-function in oncogenic Kras(G12D).

2023-08-28 | GSE192513 | GEO

Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs [SPR1108]

Project description:Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCÎ± activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance. PC9 stable cell lines expressing GFP vector or miR-371-3p were generated to study the effect of miR-371-3p in response to erlotinib treatment for RNA extraction and hybridization on Affymetrix microarrays. Stable cell lines were treated with DMSO or erlotinib for 24hrs and RNA isolated for analyzing the effect of miR-371-3p on gene expression upon erlotinib treatment.

2016-08-01 | E-GEOD-83120 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data