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Overexpressed kinetochore genes are used by cancer cells as genome destabilizers and transformation catalysts.
Aldwaik, Reem Kamal; Shian, Denen; Thapa, Roshina; Vasudevan, Swetha; Ashqar, Mimi Abo-Ayoub; Reich, Eli; Kravchenko-Balasha, Nataly; Klutstein, Michael.
Afiliación
  • Aldwaik RK; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Shian D; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Thapa R; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Vasudevan S; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Ashqar MA; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Reich E; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel.
  • Kravchenko-Balasha N; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel. Electronic address: natalyk@ekmd.huji.ac.il.
  • Klutstein M; The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem 91120, Israel. Electronic address: michaelk@ekmd.huji.ac.il.
Transl Oncol ; 34: 101703, 2023 Aug.
Article en En | MEDLINE | ID: mdl-37295219
Cancer cells have an altered transcriptome, which contributes to their abnormal behavior. Many tumors have high levels of kinetochore genes, which play important roles in genome stability. This overexpression could be utilized to destabilize cancer cell genomes, however this has not been proven specifically. We investigated the link between kinetochore gene overexpression, chromosomal number variations (CNVs) and genomic instability. Data on RNA expression and CNV from 12 different cancer types were evaluated using information theory. In all cancer types, we looked at the relationship between RNA expression and CNVs. Kinetochore gene expression was found to be substantially linked with CNV levels. In all cancer types, with the exception of thyroid cancer, highly expressed kinetochore genes were enriched in the most dominant cancer-specific co-expression subnetworks characterizing the largest patient subgroups. Except for thyroid cancer, kinetochore inner protein CENPA was among the transcripts most strongly associated with CNV values in all cancer types studied, with significantly higher expression levels in patients with high CNVs than in patients with low CNVs. CENPA function was investigated further in cell models by transfecting genomically stable (HCT116) and unstable (MCF7 and HT29) cancer cell lines using CENPA overexpression vectors. This overexpression increased the number of abnormal cell divisions in the stable cancer cell line HCT116 and, to a lesser extent, in the unstable cell lines MCF7 and HT29. Overexpression improved anchorage-independent growth properties of all cell lines. Our findings suggest that overexpression of kinetochore genes in general, and CENPA in particular, can cause genomic instability and cancer progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Transl Oncol Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Transl Oncol Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos