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Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma.

ABSTRACT: Budding Uninhibited By Benzimidazoles are a group of genes encoding proteins that play central roles in spindle checkpoint during mitosis. Improper mitosis may lead to aneuploidy which is found in many types of tumors. As a key mediator in mitosis, the dysregulated expression of BUBs has been proven to be highly associated with various malignancies, such as leukemia, gastric cancer, breast cancer, and liver cancer. However, bioinformatic analysis has not been applied to explore the role of the BUBs in sarcomas. Herein, we investigate the transcriptional and survival data of BUBs in patients with sarcomas using Oncomine, Gene Expression Profiling Interactive Analysis, Cancer Cell Line Encyclopedia, Kaplan-Meier Plotter, LinkedOmics, and the Database for Annotation, Visualization and Integrated Discovery. We found that the expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas. This study implies that BUB1, BUB1B and BUB3 are potential treatment targets for patients with sarcomas and are new biomarkers for the prognosis of sarcomas.

SUBMITTER: Long Z

PROVIDER: S-EPMC8148488 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The spindle assembly checkpoint (SAC) delays anaphase onset until sister chromosomes are bound to microtubules from opposite spindle poles. Only then can dynamic microtubules produce tension across sister kinetochores. The interdependence of kinetochore attachment and tension has proved challenging to understanding SAC mechanisms. Whether the SAC responds simply to kinetochore attachment or to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relation between attachment and tension. We developed a Taxol-sensitive yeast model to reduce tension in fully assembled spindles. Our results show that low tension on bipolar-attached kinetochores delays anaphase onset, independent of detachment. The delay is transient relative to that imposed by unattached kinetochores. Furthermore, it is mediated by Bub1 and Bub3, but not Mad1, Mad2, and Mad3 (BubR1). Our results demonstrate that reduced tension delays anaphase onset via a signal that is temporally and mechanistically distinct from that produced by unattached kinetochores.

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Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis.

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Yeast Fin1-PP1 dephosphorylates an Ipl1 substrate, Ndc80, to remove Bub1-Bub3 checkpoint proteins from the kinetochore during anaphase.

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