Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

ABSTRACT: Colorectal cancer aberrant repeat RNA expression can be therapeutically targeted with reverse transcriptase inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199097 | GEO | 2022/03/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer.

Project description:Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.SignificanceColorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1397.

| S-EPMC9167735 | biostudies-literature

Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Project description:Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

| PRJNA818339 | ENA

Mass spectrum for identifying the interacting proteins of telomerase reverse transcriptase

Project description:The 293T cells overexpressing human telomerase reverse transcriptase (hTERT) were lysed and co-immunoprecipitation was performed using hTERT antibody. Then protein mass spectrum was conducted in order to identify the hTERT-interacting proteins.

2024-01-26 | PXD048859 | Pride

Reverse transcriptase inhibitors in Aicardi-Goutières syndrome

Project description:Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous encephalopathy whose pathology is linked to an abnormal type I interferon response induced by self-derived nucleic acids. Data indicate that endogenous retroelements represent one source of interferon-stimulatory self-nucleic acid. No effective therapies are available for this disorder. In this pilot study involving patients with AGS due to mutations in TREX1, RNASEH2A, RNASEH2B or SAMHD1 three nucleoside analogue reverse transcriptase inhibitors (RTIs) were administered over 12 months. Transcription profiling was done by RNA-seq.

2018-12-12 | E-MTAB-7087 | biostudies-arrayexpress

Reverse transcriptase inhibitors in Aicardi-Goutières syndrome

Project description:Reverse transcriptase inhibitors in Aicardi-Goutières syndrome

| PRJEB27958 | ENA

Evolution of a Reverse Transcriptase to Map N1-Methyladenosine in Human mRNA

Project description:Chemical modifications on mRNA are increasingly recognized as a critical regulatory layer of the flow of genetic information, but quantitative tools to monitor RNA modifications in a whole-transcriptome and site-specific manner are lacking. Here we describe a versatile directed evolution platform that rapidly selects for reverse transcriptases that install mutations during reverse transcription at sites of a given type of RNA modification, allowing for site-specific identification of the modification. To develop and validate the platform, we evolved the HIV-1 reverse transcriptase against N1-methyladenosine (m1A). Iterative rounds of selection yielded reverse transcriptases with both robust read-through and high mutation rates at m1A sites. We apply the evolved reverse transcriptase to identify thousands of statistically confident m1A sites in human mRNA, some of which can be detected in antibody-free RNA-seq libraries. Together, this work develops and validates the reverse transcriptase evolution platform and provides new tools, analysis methods, and datasets to study m1A biology.

2019-09-24 | GSE123365 | GEO

Sequencing of Echinococcus multilocularis telomerase reverse transcriptase gene

Project description:Sequencing of Echinococcus multilocularis telomerase reverse transcriptase gene

| PRJEB32610 | ENA

Enhanced cardiac repair by human telomerase reverse transcriptase over-expression in human cardiac mesenchymal stem cells

Project description:RNA-seq profiling of gene expression of human telomerase reverse transcriptase (hTERT)-expressing human cardiac mesenchymal stem cells.

2020-03-31 | GSE112297 | GEO

Mutant IDH1 inhibition activates tumor immunity via endogenous reverse transcriptase and dsDNA sensing

Project description:Isocitrate Dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores anti-tumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show striking, selective hypermethylation and silencing of the cytoplasmic dsDNA sensor, CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase activates cGAS, triggering viral mimicry and stimulating anti-tumor immunity. Thus, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous reverse transcriptase activity to the mechanism of action of an FDA-approved oncology drug.

2024-04-24 | GSE265829 | GEO

Mutant IDH1 inhibition induces reverse transcriptase and dsDNA sensing to activate tumor immunity

2024-04-24 | GSE265788 | GEO