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The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
by
Cabezas, Mario Román
, Fodde, Riccardo
, Shimizu, Masayoshi
, van den Bosch, Thierry P. P.
, Verrijzer, C. Peter
, Verhagen, Mathijs P.
, Koljenović, Senada
, Chen, Meng
, Stabile, Roberto
, Hardillo, Jose A.
, Baatenburg de Jong, Robert J.
, Tucci, Francesco A.
, van der Steen, Berdine
, Nigg, Alex L.
, Ivan, Cristina
, De Herdt, Maria J.
, Calin, George A.
in
13/1
/ 13/105
/ 13/106
/ 13/31
/ 13/44
/ 13/51
/ 13/95
/ 14/32
/ 3' Untranslated regions
/ 38/61
/ 631/337/176
/ 631/67/69
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Cell cycle
/ Cell differentiation
/ Cell Line, Tumor
/ Cell Proliferation - genetics
/ Cyclin-dependent kinase
/ Cyclin-dependent kinase 2
/ Cyclin-Dependent Kinase Inhibitor Proteins - metabolism
/ Cyclin-dependent kinases
/ Deacetylation
/ DNA microarrays
/ DOC1 protein
/ Embryo cells
/ Epigenetics
/ Gene Expression Regulation, Neoplastic
/ Genes, Tumor Suppressor
/ Histones
/ Humans
/ Immunology
/ Kinases
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ miRNA
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - pathology
/ mRNA
/ Oral cancer
/ Oral carcinoma
/ Oral cavity
/ Oral squamous cell carcinoma
/ Proteins
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - pathology
/ Stem cells
/ Tumor cell lines
/ Tumor suppressor genes
/ Tumor Suppressor Proteins - genetics
/ Tumors
2023
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The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
by
Cabezas, Mario Román
, Fodde, Riccardo
, Shimizu, Masayoshi
, van den Bosch, Thierry P. P.
, Verrijzer, C. Peter
, Verhagen, Mathijs P.
, Koljenović, Senada
, Chen, Meng
, Stabile, Roberto
, Hardillo, Jose A.
, Baatenburg de Jong, Robert J.
, Tucci, Francesco A.
, van der Steen, Berdine
, Nigg, Alex L.
, Ivan, Cristina
, De Herdt, Maria J.
, Calin, George A.
in
13/1
/ 13/105
/ 13/106
/ 13/31
/ 13/44
/ 13/51
/ 13/95
/ 14/32
/ 3' Untranslated regions
/ 38/61
/ 631/337/176
/ 631/67/69
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Cell cycle
/ Cell differentiation
/ Cell Line, Tumor
/ Cell Proliferation - genetics
/ Cyclin-dependent kinase
/ Cyclin-dependent kinase 2
/ Cyclin-Dependent Kinase Inhibitor Proteins - metabolism
/ Cyclin-dependent kinases
/ Deacetylation
/ DNA microarrays
/ DOC1 protein
/ Embryo cells
/ Epigenetics
/ Gene Expression Regulation, Neoplastic
/ Genes, Tumor Suppressor
/ Histones
/ Humans
/ Immunology
/ Kinases
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ miRNA
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - pathology
/ mRNA
/ Oral cancer
/ Oral carcinoma
/ Oral cavity
/ Oral squamous cell carcinoma
/ Proteins
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - pathology
/ Stem cells
/ Tumor cell lines
/ Tumor suppressor genes
/ Tumor Suppressor Proteins - genetics
/ Tumors
2023
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The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
by
Cabezas, Mario Román
, Fodde, Riccardo
, Shimizu, Masayoshi
, van den Bosch, Thierry P. P.
, Verrijzer, C. Peter
, Verhagen, Mathijs P.
, Koljenović, Senada
, Chen, Meng
, Stabile, Roberto
, Hardillo, Jose A.
, Baatenburg de Jong, Robert J.
, Tucci, Francesco A.
, van der Steen, Berdine
, Nigg, Alex L.
, Ivan, Cristina
, De Herdt, Maria J.
, Calin, George A.
in
13/1
/ 13/105
/ 13/106
/ 13/31
/ 13/44
/ 13/51
/ 13/95
/ 14/32
/ 3' Untranslated regions
/ 38/61
/ 631/337/176
/ 631/67/69
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell Biology
/ Cell Culture
/ Cell cycle
/ Cell differentiation
/ Cell Line, Tumor
/ Cell Proliferation - genetics
/ Cyclin-dependent kinase
/ Cyclin-dependent kinase 2
/ Cyclin-Dependent Kinase Inhibitor Proteins - metabolism
/ Cyclin-dependent kinases
/ Deacetylation
/ DNA microarrays
/ DOC1 protein
/ Embryo cells
/ Epigenetics
/ Gene Expression Regulation, Neoplastic
/ Genes, Tumor Suppressor
/ Histones
/ Humans
/ Immunology
/ Kinases
/ Life Sciences
/ MicroRNAs
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ miRNA
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - pathology
/ mRNA
/ Oral cancer
/ Oral carcinoma
/ Oral cavity
/ Oral squamous cell carcinoma
/ Proteins
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - pathology
/ Stem cells
/ Tumor cell lines
/ Tumor suppressor genes
/ Tumor Suppressor Proteins - genetics
/ Tumors
2023
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The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
Journal Article
The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs
2023
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Overview
Cyclin-dependent kinase 2-associated protein 1 (
CDK2AP1
; also known as deleted in oral cancer or
DOC1
) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the
DOC1
acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much
CDK2AP1
mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1–3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/105
/ 13/106
/ 13/31
/ 13/44
/ 13/51
/ 13/95
/ 14/32
/ 38/61
/ Biomedical and Life Sciences
/ Cell Proliferation - genetics
/ Cyclin-Dependent Kinase Inhibitor Proteins - metabolism
/ Gene Expression Regulation, Neoplastic
/ Histones
/ Humans
/ Kinases
/ miRNA
/ mRNA
/ Oral squamous cell carcinoma
/ Proteins
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - pathology
/ Tumor Suppressor Proteins - genetics
/ Tumors
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