Downregulation of DCC sensitizes multiple myeloma cells to bortezomib treatment

Rodrigues‑Junior,Dorival   Mendes; Biassi,Thaís  Priscila; de Albuquerque,Gabriela   Estrela; Carlin,Viviane; Buri,Marcus   Vinicius; Machado‑Junior,Joel; Vettore,Andre  Luiz

doi:10.3892/mmr.2019.10142

Downregulation of DCC sensitizes multiple myeloma cells to bortezomib treatment

Authors:
- Dorival Mendes Rodrigues‑Junior
- Thaís Priscila Biassi
- Gabriela Estrela de Albuquerque
- Viviane Carlin
- Marcus Vinicius Buri
- Joel Machado‑Junior
- Andre Luiz Vettore
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Affiliations: Department of Biological Sciences, Laboratório de Biologia Molecular do Câncer, UNIFESP, Universidade Federal de São Paulo, Campus Diadema, São Paulo 04039‑032, Brazil, Department of Biochemistry, Insitute of Pharmacology, Universidade Federal de São Paulo, Campus São Paulo, São Paulo 04044‑020, Brazil
Published online on: April 9, 2019 https://doi.org/10.3892/mmr.2019.10142
Pages: 5023-5029

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Abstract

Multiple myeloma (MM) is an incurable disease; a better understanding of the molecular aspects of this hematological malignancy could contribute to the development of new treatment strategies and help to improve the survival rates of patients with MM. Previously, the methylation status of the deleted in colorectal cancer (DCC) gene was correlated with the survival rate of patients with MM, thus the main goal of this study was to understand DCC contribution to MM tumorigenesis, and to assess the impact of DCC inhibition in the MM response to treatment with bortezomib. Our results demonstrated that hypermethylation of the DCC promoter inhibits gene expression, and DCC silencing is significantly correlated with a reduction in cell viability and an increase in cell death induced by bortezomib. In conclusion, our results suggested that hypermethylation is an important mechanism of DCC expression regulation in MM and that the absence of DCC contributes to the enhanced sensitivity to treatment with bortezomib.

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