A unique spectrum of spontaneous tumors in Dino knockout mice identifies tissue-specific requirements for tumor suppression Journal Article
| Authors: | Marney, C. B.; Anderson, E. S.; Baum, R.; Schmitt, A. M. |
| Article Title: | A unique spectrum of spontaneous tumors in Dino knockout mice identifies tissue-specific requirements for tumor suppression |
| Abstract: | Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino(-/-) mice develop significantly more malignant tumors than Dino(+/+) littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence of lymphomas and sarcomas in Dino(-/-) mice is similar to that of mice with p53 loss, important distinctions emerged. p53-null mice predominantly develop T cell lymphomas; however, no spontaneous T cell lymphoma was observed in Dino(-/-) mice. Rather than being a phenocopy of the p53-null tumor spectrum, spontaneous tumors in Dino(-/-) mice resemble the spectrum of human cancers in which DINO is recurrently silenced by methylation in a manner that is mutually exclusive with TP53 alterations, suggesting that similar tissues in human and mouse require DINO for tumor suppression. Consistent with a tissue-specific role for Dino in tumor suppression, loss of Dino had no impact on the development of radiation-induced T cell lymphoma and oncogene-driven medulloblastoma, tumors that are accelerated by the loss of p53. Taken together, these data indicate that Dino serves as a potent tumor suppressor molecule specific to a select subset of tissues in mice and humans. |
| Keywords: | mutation; apoptosis; tumorigenesis; lymphoma; tumor; p53; spectrum; tumor suppression; dna-damage; absence; network; puma; lncrna; dino; long non-coding rna; lncrna malat1 |
| Journal Title: | Cells |
| Volume: | 11 |
| Issue: | 11 |
| ISSN: | 2073-4409 |
| Publisher: | MDPI |
| Date Published: | 2022-06-01 |
| Language: | English |
| ACCESSION: | WOS:000808706800001 |
| DOI: | 10.3390/cells11111818 |
| PROVIDER: | wos |
| PMCID: | PMC9180304 |
| PUBMED: | 35681513 |
| Notes: | Article -- 1818 -- Source: Wos |
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