Patrícia M A Silva1, Maria Leonor Delgado1, Nilza Ribeiro1, Cláudia Florindo2,3, Álvaro A Tavares2,3, Diana Ribeiro1, Carlos Lopes1,4, Barbas do Amaral1,5, Hassan Bousbaa1,6, Luís Silva Monteiro1. 1. Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, CESPU, Gandra, Portugal. 2. Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal. 3. Departamento Ciências Biomédicas e Medicina, University of Algarve, Faro, Portugal. 4. Molecular Pathology and Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), Porto University, Porto, Portugal. 5. Stomatology Department, Oporto Hospitalar Centre, Hospital de Santo António, Porto, Portugal. 6. Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Matosinhos, Portugal.
Abstract
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.
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.
Authors: Tatiana V Kudryashova; Swati Dabral; Soni S Pullamsetti; Elena A Goncharova; Sreenath Nayakanti; Arnab Ray; Dmitry A Goncharov; Theodore Avolio; Yuanjun Shen; Analise Rode; Andressa Pena; Lifeng Jiang; Derek Lin; Jeffrey Baust; Timothy N Bachman; Johannes Graumann; Clemens Ruppert; Andreas Guenther; Mario Schmoranzer; Yann Grobs; Sarah Eve Lemay; Eve Tremblay; Sandra Breuils-Bonnet; Olivier Boucherat; Ana L Mora; Horace DeLisser; Jing Zhao; Yutong Zhao; Sébastien Bonnet; Werner Seeger Journal: Circ Res Date: 2022-02-07 Impact factor: 17.367
Authors: Xuejiao Ren; Qingning Zhang; Wenyan Guo; Lan Wang; Tao Wu; Wei Zhang; Ming Liu; Dezhi Kong Journal: Front Pharmacol Date: 2022-08-22 Impact factor: 5.988