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Open Access 01-12-2019 | Human Papillomavirus | Primary research

Transregulation of microRNA miR-21 promoter by AP-1 transcription factor in cervical cancer cells

Authors: Sacnite del Mar Díaz-González, Eduardo Daniel Rodríguez-Aguilar, Angélica Meneses-Acosta, Viviana Valadez-Graham, Jessica Deas, Claudia Gómez-Cerón, Carlos Alberto Tavira-Montalván, Alitzel Arizmendi-Heras, Julián Ramírez-Bello, Mario Enrique Zurita-Ortega, Berenice Illades-Aguiar, Marco Antonio Leyva-Vázquez, Gloria Fernández-Tilapa, Víctor Hugo Bermúdez-Morales, Vicente Madrid-Marina, Mauricio Rodríguez-Dorantes, Carlos Pérez-Plasencia, Oscar Peralta-Zaragoza

Published in: Cancer Cell International | Issue 1/2019

Abstract

Background

Gene expression profiles have demonstrated that miR-21 expression is altered in almost all types of cancers and it has been classified as an oncogenic microRNA. Persistent HPV infection is the main etiologic agent in cervical cancer and induces genetic instability, including disruption of microRNA gene expression. In the present study, we analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells.

Methods

To identify that c-Fos and c-Jun regulate the expression of miR-21 we performed RT-qPCR and western blot assays. We analyzed the interaction of AP-1 with miR-21 promoter by EMSA and ChIP assays and determined the mechanism of its regulation by reporter construct plasmids. We identified the nuclear translocation of c-Fos and c-Jun by immunofluorescence microscopy assays.

Results

We demonstrated that c-Fos and c-Jun proteins are expressed and regulate the expression of miR-21 in cervical cancer cells. DNA sequence analysis revealed the presence of AP-1 DNA-binding sites in the human miR-21 promoter region. EMSA analyses confirmed the interactions of the miR-21 upstream transcription factor AP-1. ChIP assays further showed the binding of c-Fos to AP-1 sequences from the miR-21 core promoter in vivo. Functional analysis of AP-1 sequences of miR-21 in reporter plasmids demonstrated that these sequences increase the miR-21 promoter activation.

Conclusions

Our findings suggest a physical interaction and functional cooperation between AP-1 transcription factor in the miR-21 promoter and may explain the effect of AP-1 on miR-21 gene expression in cervical cancer cells.

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Title: Transregulation of microRNA miR-21 promoter by AP-1 transcription factor in cervical cancer cells
Authors: Sacnite del Mar Díaz-González
Eduardo Daniel Rodríguez-Aguilar
Angélica Meneses-Acosta
Viviana Valadez-Graham
Jessica Deas
Claudia Gómez-Cerón
Carlos Alberto Tavira-Montalván
Alitzel Arizmendi-Heras
Julián Ramírez-Bello
Mario Enrique Zurita-Ortega
Berenice Illades-Aguiar
Marco Antonio Leyva-Vázquez
Gloria Fernández-Tilapa
Víctor Hugo Bermúdez-Morales
Vicente Madrid-Marina
Mauricio Rodríguez-Dorantes
Carlos Pérez-Plasencia
Oscar Peralta-Zaragoza
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Human Papillomavirus
Cervical Cancer
Cervical Cancer
Published in: Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-019-0931-x

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