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Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC

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Pathology & Oncology Research

Abstract

Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

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Fig. 1: HIF-1α and miR-210 expression in patients with OSCC primary lesion.
Fig. 2: Effect of Radiation and hypoxia in OSCC migration and death under hypoxic conditions.
Fig. 3: Proteomic analyses.
Fig. 4: Effect of radiation and hypoxia on HIF-1α, miR-210, LDH and PDH levels in OSCC cells.
Fig. 5: HIF-1α, miR-210 and LDH expression systemic in patients with OSCC submitted to radiotherapy.

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Acknowledgements

We thank the facility Laboratório Nacional de Biociências LNBio CNPEM-Brazil for the mass spectrometry analysis. We want to thank Bianca A. Pauletti in especial for technical assistance in mass spectrometry analysis.

Funding

This study was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Instituto Federal de Educação, Ciência e Tecnologia do Norte de Minas Gerais (IFNMG) and the Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Dr. Guimarães, Dr. Gomez, Dr. Santos and Dr. de Paula are research fellows of the CNPq.

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  1. Marcela Gonçalves de Souza, Sabrina Ferreira de Jesus and Eloá Mangabeira Santos contributed equally to this work.

Authors and Affiliations

  1. Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil

    Marcela Gonçalves de Souza, Sabrina Ferreira de Jesus, Eloá Mangabeira Santos, Emisael Stenio Batista Gomes, Luiz Henrique da Silveira, Alfredo Maurício Batista de Paula, Lucyana Conceição Farias & André Luiz Sena Guimarães

  2. Hospital Dilson Godinho, Montes Claros, Minas Gerais, Brazil

    Arlen de Paulo Santiago Filho & André Luiz Sena Guimarães

  3. Instituto Federal de Educação, Ciência e Tecnologia do Norte de Minas Gerais (IFNMG), Araçuaí, Minas Gerais, Brazil

    Eliane Macedo Sobrinho Santos

  4. Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil

    Sérgio Henrique Sousa Santos

  5. Hospital Universitário Clemente Faria, Laboratório de Pesquisa em Saúde, Universidade Estadual de Montes Claros, 562 Av. Cula Mangabeira Santo Expedito, Montes Claros, MG, 39401-001, Brazil

    André Luiz Sena Guimarães

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  1. Marcela Gonçalves de Souza
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Correspondence to André Luiz Sena Guimarães.

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Ethical approval for this study was obtained from the Institutional Review Board, and a signed informed consent form was obtained from all patients (process number 62425316.0.0000.5146).

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de Souza, M.G., de Jesus, S.F., Santos, E.M. et al. Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC. Pathol. Oncol. Res. 26, 433–442 (2020). https://doi.org/10.1007/s12253-018-0517-2

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