Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [RNA-Seq]

ABSTRACT: Identification and characterization of novel mechanisms driving melanoma metastases and ways to target them are paramount for the development of effective treatment modalities. We demonstrated that higher Polr1a levels correlate with increased metastasis and reduced survival in patients. In this study, we evaluated the effect of Polr1a knockdown on gene expression in melanoma cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE302801 | GEO | 2026/06/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.

Project description:Identification and characterization of novel mechanisms driving melanoma metastases and ways to target them are paramount for the development of effective treatment modalities. We demonstrated that higher Polr1a levels correlate with increased metastasis and reduced survival in patients. In this study, we evaluated the effect of Polr1a knockdown on gene expression in melanoma cells.

2026-06-11 | GSE314397 | GEO

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [Ribo-Seq]

2026-06-11 | GSE302802 | GEO

Heterozygous variants in POLR1A cause diverse human phenotypes

Project description:Heterozygous pathogenic variants in POLR1A were identified as the cause of Acrofacial Dysostosis, Cincinnati-type in 2015. Craniofacial anomalies reminiscent of Treacher Collins syndrome were the predominant phenotype observed in the first 3 affected individuals. We have subsequently identified 17 additional individuals with 12 unique (11 novel) heterozygous variants in POLR1A and observed numerous additional phenotypes including developmental delay, infantile spasms, and structural cardiac defects. To understand the pathogenesis of this pleiotropy, we created an allelic series of POLR1A using a combination of in vivo (mouse) and in vitro models. We describe distinct spatiotemporal requirements for Polr1a during mouse embryogenesis and identify a requirement for Polr1a for survival of pre migratory and migratory neural crest cells, forebrain precursors, and the second heart field. We used CRISPR/Cas9 to recapitulate two human alleles in mouse, demonstrating pathogenicity of one and likely benign nature of the other. Our work greatly expands the phenotype of human POLR1A-related disorders, provides new evidence of reduced penetrance and variable expression of POLR1A heterozygous variants, and demonstrates a multi-faceted approach to characterize and define pathogenicity of variants.

2022-08-15 | GSE206197 | GEO

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.

Project description:In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.

| PRJNA1390815 | ENA

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [Ribo-Seq]

Project description:In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [Ribo-Seq]

| PRJNA1292197 | ENA

In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [RNA-Seq]

Project description:In vivo CRISPR knockout screen reveals Polr1a as a key driver and a potential therapeutic target for melanoma metastasis [RNA-Seq]

| PRJNA1292189 | ENA

Novel biallelic mutations in POLR1A: expansion of the phenotype and insight into the molecular mechanism

Project description:The eukaryotic genome is transcribed by three RNA polymerases (Pol) I, II and III; each transcribing different classes of RNAs. Pol I transcribes ribosomal DNA and produces the polycistronic rRNA 47S, which releases 28S, 18S and 5.8S rRNAs. Heterozygous mutations in the Pol I subunit POLR1A have been described in three patients presenting with Acrofacial Dysostosis, Cincinnati Type (MIM 616462), while a homozygous mutation in POLR1A was identified in two siblings, presenting developmental regression and several brain anomalies. We present three patients with homozygous mutations in POLR1A. Patient 1, a Norwegian male homozygous for POLR1A p.T642N, presented severe neurodegeneration with epilepsy, and died at 16 years of age. Patient 2, a 5.4-years-old Mexican male homozygous for POLR1A p.R667H, presented with severe neurodegeneration, epilepsy, and skeletal anomalies. Patient 3, a 2-year-old Dutch girl homozygous for POLR1A p.T642N, manifested severe global developmental delay, and brain anomalies. Structure superimposition of POLR1A wild-type and POLR1A T642N or R667H suggested a possible abnormal interaction between POLR1A and POLR2H. In vitro experiments showed that POLR1A T642N has higher transcriptional activity, abnormal rRNA processing, increased autophagy, deprotected telomeres, and reduced levels of p53. Proteomics analysis of patients 1 supported these findings, identifying dysfunction of pathways related to protein synthesis, ubiquitination, phagosome activities, and cell survival. In conclusion, we expand the phenotype of this rare disease and document a transcriptional defect affecting multiple processes, which impact cell survival.

2023-10-24 | PXD017431 | Pride

Heterozygous variants in POLR1A cause diverse human phenotypes

Project description:Heterozygous variants in POLR1A cause diverse human phenotypes

| PRJNA849583 | ENA

Molecular profiling of driver events in metastatic uveal melanoma

Project description:Uveal melanoma (UM) is a rare form of melanoma with a genetics and immunology that is different from skin melanoma. Previous studies have identified genetic driver events of early stage disease when the tumor is confined to the eye. In this study, we have characterized genomic events in UM metastases using whole-genome and RNA sequencing from thirty-two and twenty-eight patients, respectively, and profiled individual tumor infiltrating lymphocytes in a number of the metastases. We find that 91% of the patients have metastases carrying inactivating events in the tumor suppressor BAP1 and this coincided with somatic alterations in GNAQ, GNA11, CYSLTR2, PLCB4, SF3B1 and/or CDKN2A. Mutational signature analysis revealed a rare subset of tumors with prominent signs of UV damage, associated with outlier mutational burden. We study copy number variations (CNV) and find overrepresented events, some of which were not altered in matched primary eye tumors. A focused siRNA screen identified functionally significant genes of some of the segments recurrently gained. We reintroduced a functional copy of BAP1 into a patient-derived BAP1 deficient tumor cell line and found broad transcriptomic changes of genes associated with subtype distinction and prognosis in primary UM. Lastly, our analysis of the immune microenvironments of metastases revealed a presence of tumor-reactive T cells. However, a large fraction expressed the immune checkpoint receptors such as TIM-3, TIGIT and LAG3. These results provide an updated view of genomic events represented in metastatic UM and immune interactions in advanced lesions.

2020-03-18 | PXD017743 | Pride

Expression of neural crest markers GLDC and ERRFI1 is correlated with melanoma prognosis

Project description:Regulation of particular genes during the formation of neural crest (NC) cells is also described during progression of malignant melanoma. In this context it is of paramount importance to develop neural crest models allowing the identification of candidate genes, which could be used as biomarkers for melanoma prognosis. Here, we used a human iPSC-based approach to present novel NC-associated genes, expression of which was upregulated in melanoma. A list of 8 candidate genes, based on highest upregulation, was tested for prognostic value in a tissue microarray analysis containing samples from advanced melanoma (good versus bad prognosis) as well as from high-risk primary melanomas (early metastasizing versus non or late-metastasizing). CD271, GLDC and ERRFI1 showed significantly higher expression in metastatic patients who died early than the one who survived at least 30 months. In addition, GLDC and TWIST showed a significant higher IHC score in primary melanomas from patients who developed metastases within 12 months versus those who did not develop metastases in 30 months. In conclusion, our iPSC-based study reveals a significant association of NC marker GLDC protein expression with melanoma prognosis.

2019-02-07 | GSE123686 | GEO

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