Comprehensive transcriptomic profiling of liver cancer identifies histone and PTEN are major regulators of scutellarein-induced anti-tumor activity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE232800 | GEO | 2023/06/15
REPOSITORIES: GEO
Similar Datasets
Project description:Worldwide, liver cancer is the most frequent fatal malignancy. Liver cancer prognosis is poor because patients frequently receive advanced-stage diagnoses. The current study aimed to establish the potential pharmacological targets and the biological networks of scutellarein (SCU) in liver cancer, a natural product known to have low toxicity and side effects. To identify the differentially expressed genes between SCU-treated and SCU-untreated HepG2 cells, RNA sequencing (RNA-seq) was carried out. A total of 463 genes were revealed to have differential expression, of which 288 were upregulated and 175 were downregulated in the group that had received SCU treatment compared with a control group. Gene Ontology (GO) enrichment analysis of associated biological process terms revealed they were mostly involved in the regulation of protein heterodimerization activity and nucleosomes. Interaction of protein-protein network analysis using Search Tool for the Retrieval of Interacting Genes/Proteins resulted in two crucial interacting hub targets; namely, histone H1-4 and protein tyrosine phosphatase receptor type C. Additionally, the crucial targets were validated using western blotting. Overall, the present study demonstrated that the use of RNA-seq data, with bioinformatics tools, can provide a valuable resource to identify the pharmacological targets that could have important biological roles in liver cancer.
| S-EPMC10823307 | biostudies-literature
Project description:We applied next-generation sequencing to analyse changes in the expression of Dclk1 gene isoforms in the brain in response to several psychoactive drugs with diverse pharmacological mechanisms of action. We used bioinformatics tools to define the range and levels of Dclk1 transcriptional regulation in the mouse nucleus accumbens and prefrontal cortex
2018-07-17 | GSE117174 | GEO
Project description:miRNAs are small non-coding regulatory RNAs that play important functions in the regulation of gene expression at the post-transcriptional level by targeting mRNAs for degradation or by inhibiting protein translation. Eugenia uniflora is a plant native to tropical America with pharmacological and ecological importance without previous studies about its gene expression and regulation. To date, there is not miRNAs reported in species of Myrtaceae. A small RNA library was constructed to identify miRNAs in Eugenia uniflora. Solexa technology was used to perform high throughput sequencing of the library and the data obtained was analysed using bioinformatics tools. From 14,489,131 clean reads, we obtained 1,852,722 small RNAs representing 45 known miRNA families that have been identified in other plant species. Further analysis using contigs assembled from Illumina mRNA sequencing of leaves from the same individual allowed the prediction of secondary structures of 25 known and 17 novel miRNAs. Potential targets were predicted for the most abundant mature miRNAs in the identified pre-miRNAs based on sequence homology. This study provide the first large scale identification of miRNAs and their potential targets of a species from Myrtaceae without previous genomic sequence resources. Our study provides more information about the evolutionary conservation of the regulatory network of miRNAs in plants and highlights the miRNAs species-specific. microRNA profiles in 1 leaf library of Eugenia uniflora by deep sequencing (Illumina HiSeq2000)
2013-01-07 | E-GEOD-38211 | biostudies-arrayexpress
Project description:miRNAs are small non-coding regulatory RNAs that play important functions in the regulation of gene expression at the post-transcriptional level by targeting mRNAs for degradation or by inhibiting protein translation. Eugenia uniflora is a plant native to tropical America with pharmacological and ecological importance without previous studies about its gene expression and regulation. To date, there is not miRNAs reported in species of Myrtaceae. A small RNA library was constructed to identify miRNAs in Eugenia uniflora. Solexa technology was used to perform high throughput sequencing of the library and the data obtained was analysed using bioinformatics tools. From 14,489,131 clean reads, we obtained 1,852,722 small RNAs representing 45 known miRNA families that have been identified in other plant species. Further analysis using contigs assembled from Illumina mRNA sequencing of leaves from the same individual allowed the prediction of secondary structures of 25 known and 17 novel miRNAs. Potential targets were predicted for the most abundant mature miRNAs in the identified pre-miRNAs based on sequence homology. This study provide the first large scale identification of miRNAs and their potential targets of a species from Myrtaceae without previous genomic sequence resources. Our study provides more information about the evolutionary conservation of the regulatory network of miRNAs in plants and highlights the miRNAs species-specific. mRNA profiles in 1 leaf library of Eugenia uniflora by deep sequencing (Illumina HiSeq2000)
2013-01-07 | E-GEOD-38210 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signalling pathways, extracellular remodelling, metabolic, chromatin remodelling and transcriptional regulators. The study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.
2015-06-09 | GSE69663 | GEO
Project description:Recent studies hint that endogenous dsRNA plays an unexpected role in cellular signaling. However, a complete understanding of the mechanisms underlying endogenous dsRNA signaling is hindered by an incomplete annotation of dsRNA-producing genes. In order to identify all dsRNAs expressed in C. elegans, we developed a bioinformatics pipeline that identifies dsRNA by detecting clustered RNA editing sites, which are strictly limited to long dsRNA substrates of Adenosine Deaminases that act on RNA (ADAR). Using a combination of alignment algorithms to map both unique and repetitive reads, we detected as many as 664 editing-enriched regions (EERs). Most EERs were associated with protein-coding genes, with ~1.7% of all C. elegans mRNAs containing an EER, located primarily in introns and 3’UTRs. Introns having an embedded EER were up to 9-fold longer than the average C. elegans intron. A significant fraction of EERs were located less than 1000 base pairs downstream of protein-coding genes and likely represent a previously undetected population of edited 3’UTRs. Many EERs are predicted to possess strong internal secondary structures as well as sequence complementarity with other EERs, indicative of both intramolecular and intermolecular dsRNAs. In addition to numerous EERs associated with coding genes, we identified a population of prospective noncoding EERs, distant from protein coding genes with no overlapping genome annotation and little to no coding potential. By combining next-generation RNA sequencing with freely available bioinformatics tools, our workflow provides an easily accessible approach for the identification of dsRNAs, and more importantly, a comprehensive catalogue of the C. elegans dsRNAome.
2015-04-09 | GSE61564 | GEO
Project description:Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known how mutant NPM1 (NPM1mut) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1mut AML. Using a CRISPR-Cas9 genome editing domain screen, we show NPM1mut AML to be exceptionally dependent on the menin binding site in MLL1. Pharmacological small-molecule inhibition of the menin-MLL protein interaction had profound anti-leukemic activity in human and murine models of NPM1mut AML in vitro and in vivo. Combined pharmacological inhibition of menin-MLL and DOT1L resulted in dramatic suppression of HOX and FLT3 expression, induction of differentiation, and superior activity against NPM1mut leukemia. Together, MLL1 and DOT1L are chromatin regulators that control HOX, MEIS1 and FLT3 expression and are therapeutic targets in NPM1mut AML. Combinatorial small-molecule inhibition has synergistic on target activity and constitutes a novel therapeutic concept for this common AML subtype. RNA sequencing data of the human AML cell lines OCI-AML2 and OCI-AML3 comparing EPZ004777 [10µM] drug treatment versus DMSO vehicle control; experiments performed in biological triplicates.
2016-08-22 | E-GEOD-85107 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signalling pathways, extracellular remodelling, metabolic, chromatin remodelling and transcriptional regulators. The study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart. 6 samples (CHL1, CHL2, CHL3, CHL4, CHL5, CHL6)
2015-06-09 | E-GEOD-69663 | biostudies-arrayexpress
Project description:The development of antibiotic tolerance is believed to be a major factor in the lengthy duration of current tuberculosis therapies. In the current study, we have modeled antibiotic tolerance in vitro by exposing Mycobacterium tuberculosis to two distinct stress conditions: progressive hypoxia and nutrient starvation [phosphate-buffered saline (PBS)]. We then studied the bacterial transcriptional response using RNA-seq and employed a bioinformatics approach to identify important transcriptional regulators, which was facilitated by a novel Regulon Enrichment Test (RET). A total of 17 transcription factor (TF) regulons were enriched in the hypoxia gene set and 16 regulons were enriched in the nutrient starvation, with 12 regulons enriched in both conditions. Using the same approach to analyze previously published gene expression datasets, we found that three M. tuberculosis regulons (Rv0023, SigH, and Crp) were commonly induced in both stress conditions and were also among the regulons enriched in our data. These regulators are worthy of further study to determine their potential role in the development and maintenance of antibiotic tolerance in M. tuberculosis following stress exposure.
2018-04-03 | GSE104599 | GEO
Project description:Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nucleotides, which do not encode proteins (non-coding), yet they participate in the regulation of gene expression through multiple mechanisms in the form of RNA. A total of 51 lncRNAs and 21 mRNAs whose expression changed significantly, were identified. Five deregulated lncRNAs and five mRNAs were confirmed by quantitative real-time polymerase chain reaction (PCR) in 10 paired samples. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of the deregulated genes. Furthermore, correlated expression networks of coding-noncoding co-expression (CNC) was constructed by using bioinformatics methods. We predicted the potential targets of lncRNAs by using bioinformatics methods. In summary, novel lnRNAs were identified as potential biomarkers and therapeutic targets for POCD treatment.
2017-02-28 | GSE95426 | GEO