Objectives: Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC).
Materials And Methods: Bub3 and Spindly expression was evaluated by immunohistochemistry in 62 tissue microarrays from OSCC and by real-time PCR in OSCC cell lines and in normal human oral keratinocytes. The results were analyzed as to their clinicopathological significance. RNA interference-mediated Spindly or Bub3 inhibition was combined with cisplatin treatment, and the effect on the viability of OSCC cells was assessed.
Results: Overexpression of Bub3 and Spindly was detected in OSCC patients. High expression of Spindly, Bub3, or both was an independent prognostic indicator for cancer-specific survival and was associated with increased cellular proliferation. Accordingly, Bub3 and Spindly were upregulated in OSCC cells comparatively to their normal counterpart. Inhibition of Bub3 or Spindly was cytotoxic to OSCC cells and enhanced their chemosensitivity to cisplatin.
Conclusions: The data point out Bub3 and Spindly as potential markers of proliferation and prognosis, and highlight the potential therapeutic benefit of combining their inhibition with cisplatin.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/odi.13089 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BUBR1 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma.
Animals (Basel)
November 2022
Department of Veterinary Science of the University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal.
Chromosomal instability (CIN) plays a key role in the carcinogenesis of several human cancers and can be related to the deregulation of core components of the spindle assembly checkpoint (SAC) including BUBR1 protein kinase. These proteins have been related to tumor development and poor survival rates in human patients with oral squamous cell carcinoma (OSCC). To investigate the expression of the SAC proteins BUBR1, BUB3 and SPINDLY and also Ki-67 in canine OSCC, we performed an immunohistochemical evaluation in 60 canine OSCCs and compared them with clinical and pathological variables.
View Article and Find Full Text PDFExpression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study.
Med Oral Patol Oral Cir Bucal
November 2021
Rua Central de Gandra, 1317 4585-116 Gandra PRD, Portugal
Background: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia.
Material And Methods: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues.
[Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma].
Shanghai Kou Qiang Yi Xue
October 2020
Department of Stomatology, The Fourth Hospital of Hebei Medical University.Shijiazhuang 050011, Hebei Province, China.
Purpose: To investigate the expression and significance of Spindly and Bub3 in oral squamous cell carcinoma(OSCC).
Methods: Sixty-five patients with OSCC admitted to the Fourth Hospital of Hebei Medical University from March 2017 to March 2019 were enrolled. RT-PCR was used to detect the expression of Spindly and Bub3 mRNA in oral squamous cell carcinoma and adjacent normal tissues from the patients.
Spindly and Bub3 expression in oral cancer: Prognostic and therapeutic implications.
Oral Dis
July 2019
Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, CESPU, Gandra, Portugal.
Objectives: Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC).
Materials And Methods: Bub3 and Spindly expression was evaluated by immunohistochemistry in 62 tissue microarrays from OSCC and by real-time PCR in OSCC cell lines and in normal human oral keratinocytes.
Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore-microtubule attachments.
FEBS Lett
November 2015
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. Electronic address:
We previously reported that the spindle assembly checkpoint protein Bub3 is involved in regulating kinetochore-microtubule (KT-MT) attachments. Also, Bub3 was reported to interact with the microtubule motor protein dynein. Here we examined how this interaction contributes to KT-MT attachments.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!