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An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
by
Slack, Frank J.
, Santisteban, Pilar
, Ramírez-Moya, Julia
, Baker, Allison R.
, Gregory, Richard I.
, Miliotis, Christos
in
A-to-I editing
/ ADAR1
/ Adenosine
/ Adenosine Deaminase - metabolism
/ Alleles
/ Analysis
/ Biomedical and Life Sciences
/ Biomedicine
/ Biotechnology industry
/ Cancer
/ Cancer Research
/ CDC2 Protein Kinase - genetics
/ CDC2 Protein Kinase - metabolism
/ CDK13
/ Cell Line, Tumor
/ Cell Movement - genetics
/ Cell Proliferation
/ Cell Survival - genetics
/ Cell viability
/ Cyclin-dependent kinase
/ Cyclin-dependent kinases
/ Development and progression
/ Disease Progression
/ Editing
/ Enzymes
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene Knockdown Techniques
/ Gene Silencing
/ Genes
/ Genetic engineering
/ Genomes
/ Humans
/ Kinases
/ Localization
/ Nucleoli
/ Oncology
/ Patients
/ Plasmids
/ Protein Transport
/ RNA
/ RNA Editing
/ RNA Splicing
/ RNA-Binding Proteins - metabolism
/ RNA-mediated interference
/ Splicing
/ Thyroid cancer
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - metabolism
/ Thyroid Neoplasms - pathology
/ Transcription
/ Transcriptomes
/ Tumors
2021
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An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
by
Slack, Frank J.
, Santisteban, Pilar
, Ramírez-Moya, Julia
, Baker, Allison R.
, Gregory, Richard I.
, Miliotis, Christos
in
A-to-I editing
/ ADAR1
/ Adenosine
/ Adenosine Deaminase - metabolism
/ Alleles
/ Analysis
/ Biomedical and Life Sciences
/ Biomedicine
/ Biotechnology industry
/ Cancer
/ Cancer Research
/ CDC2 Protein Kinase - genetics
/ CDC2 Protein Kinase - metabolism
/ CDK13
/ Cell Line, Tumor
/ Cell Movement - genetics
/ Cell Proliferation
/ Cell Survival - genetics
/ Cell viability
/ Cyclin-dependent kinase
/ Cyclin-dependent kinases
/ Development and progression
/ Disease Progression
/ Editing
/ Enzymes
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene Knockdown Techniques
/ Gene Silencing
/ Genes
/ Genetic engineering
/ Genomes
/ Humans
/ Kinases
/ Localization
/ Nucleoli
/ Oncology
/ Patients
/ Plasmids
/ Protein Transport
/ RNA
/ RNA Editing
/ RNA Splicing
/ RNA-Binding Proteins - metabolism
/ RNA-mediated interference
/ Splicing
/ Thyroid cancer
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - metabolism
/ Thyroid Neoplasms - pathology
/ Transcription
/ Transcriptomes
/ Tumors
2021
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An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
by
Slack, Frank J.
, Santisteban, Pilar
, Ramírez-Moya, Julia
, Baker, Allison R.
, Gregory, Richard I.
, Miliotis, Christos
in
A-to-I editing
/ ADAR1
/ Adenosine
/ Adenosine Deaminase - metabolism
/ Alleles
/ Analysis
/ Biomedical and Life Sciences
/ Biomedicine
/ Biotechnology industry
/ Cancer
/ Cancer Research
/ CDC2 Protein Kinase - genetics
/ CDC2 Protein Kinase - metabolism
/ CDK13
/ Cell Line, Tumor
/ Cell Movement - genetics
/ Cell Proliferation
/ Cell Survival - genetics
/ Cell viability
/ Cyclin-dependent kinase
/ Cyclin-dependent kinases
/ Development and progression
/ Disease Progression
/ Editing
/ Enzymes
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Gene Knockdown Techniques
/ Gene Silencing
/ Genes
/ Genetic engineering
/ Genomes
/ Humans
/ Kinases
/ Localization
/ Nucleoli
/ Oncology
/ Patients
/ Plasmids
/ Protein Transport
/ RNA
/ RNA Editing
/ RNA Splicing
/ RNA-Binding Proteins - metabolism
/ RNA-mediated interference
/ Splicing
/ Thyroid cancer
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - metabolism
/ Thyroid Neoplasms - pathology
/ Transcription
/ Transcriptomes
/ Tumors
2021
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An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
Journal Article
An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
2021
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Overview
Background
Adenosine deaminases acting on RNA (ADARs) modify many cellular RNAs by catalyzing the conversion of adenosine to inosine (A-to-I), and their deregulation is associated with several cancers. We recently showed that A-to-I editing is elevated in thyroid tumors and that ADAR1 is functionally important for thyroid cancer cell progression. The downstream effectors regulated or edited by ADAR1 and the significance of ADAR1 deregulation in thyroid cancer remain, however, poorly defined.
Methods
We performed whole transcriptome sequencing to determine the consequences of ADAR1 deregulation for global gene expression, RNA splicing and editing. The effects of gene silencing or RNA editing were investigated by analyzing cell viability, proliferation, invasion and subnuclear localization, and by protein and gene expression analysis.
Results
We report an oncogenic function for
CDK13
in thyroid cancer and identify a new ADAR1-dependent RNA editing event that occurs in the coding region of its transcript.
CDK13
was significantly over-edited (c.308A > G) in tumor samples and functional analysis revealed that this editing event promoted cancer cell hallmarks. Finally, we show that
CDK13
editing increases the nucleolar abundance of the protein, and that this event might explain, at least partly, the global change in splicing produced by ADAR1 deregulation.
Conclusions
Overall, our data support A-to-I editing as an important pathway in cancer progression and highlight novel mechanisms that might be used therapeutically in thyroid and other cancers.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ ADAR1
/ Adenosine Deaminase - metabolism
/ Alleles
/ Analysis
/ Biomedical and Life Sciences
/ Cancer
/ CDC2 Protein Kinase - genetics
/ CDC2 Protein Kinase - metabolism
/ CDK13
/ Editing
/ Enzymes
/ Gene Expression Regulation, Neoplastic
/ Genes
/ Genomes
/ Humans
/ Kinases
/ Nucleoli
/ Oncology
/ Patients
/ Plasmids
/ RNA
/ RNA-Binding Proteins - metabolism
/ Splicing
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - metabolism
/ Thyroid Neoplasms - pathology
/ Tumors
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