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The expression of RNA helicase DDX5 is transcriptionally upregulated by calcitriol through a vitamin D response element in the proximal promoter in SiHa cervical cells

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Abstract

The DEAD box RNA helicase DDX5 is a multifunctional protein involved in the regulatory events of gene expression. Herein, we presented evidence indicating that DDX5 is transcriptionally upregulated by calcitriol, the hormonal form of vitamin D3. In silico analysis revealed the presence of two putative vitamin D response elements (VDREs) in the DDX5 promoter region. Using luciferase reporter assays, we demonstrated that the DDX5 promoter containing these putative VDREs significantly increased the luciferase activity in vitamin D receptor (VDR)-positive SiHa cells upon calcitriol treatment. Electrophoretic mobility shift assays showed the ability of VDR and retinoid X receptor to interact only with the most proximal VDRE, while chromatin immunoprecipitation analysis confirmed the occupancy of this VDRE by the VDR. Finally, we demonstrated that calcitriol significantly increased both DDX5 mRNA and protein in SiHa cells. In summary, this study shows that DDX5 gene is transcriptionally upregulated by calcitriol through a VDRE located in its proximal promoter. Given the importance of DDX5 as a master regulator of differentiation programs, our study suggests that the pro-differentiating properties of calcitriol may be related with the induction of DDX5.

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Funding

This study was funded by the Consejo Nacional de Ciencia y Tecnología (CONACyT, México), grants number 241034 and 153862 to EA and LD, respectively. CONACyT had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, 14080, Mexico, D.F., Mexico

    Ramiro José González-Duarte, Verna Cázares-Ordoñez, Lorenza Díaz, Fernando Larrea & Euclides Avila

  2. Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, 14080, Mexico, D.F., Mexico

    Víctor Ortíz

  3. School of Medicine, Universidad Nacional Autónoma de México, Circuito Interior, Ciudad Universitaria, Av. Universidad # 3000, 04510, Mexico, D.F., Mexico

    Ramiro José González-Duarte & Verna Cázares-Ordoñez

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  1. Ramiro José González-Duarte
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  2. Verna Cázares-Ordoñez
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  3. Lorenza Díaz
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  4. Víctor Ortíz
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  5. Fernando Larrea
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  6. Euclides Avila
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Correspondence to Euclides Avila.

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Disclosures

This article is part of the doctoral thesis of R.J.G.D., at Programa de Doctorado en Ciencias Biomédicas, School of Medicine, Universidad Nacional Autónoma de México (México) under a fellowship from Consejo Nacional de Ciencia y Tecnología (fellowship 207287).

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González-Duarte, R.J., Cázares-Ordoñez, V., Díaz, L. et al. The expression of RNA helicase DDX5 is transcriptionally upregulated by calcitriol through a vitamin D response element in the proximal promoter in SiHa cervical cells. Mol Cell Biochem 410, 65–73 (2015). https://doi.org/10.1007/s11010-015-2538-4

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  • DOI: https://doi.org/10.1007/s11010-015-2538-4

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