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

Autor: Del Mar Díaz-González S; Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Av. Lázaro Cárdenas S/N, Col. Haciendita, 39070 Chilpancingo, Guerrero Mexico., Rodríguez-Aguilar ED; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Meneses-Acosta A; 3Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Autonomous University of Morelos State, Av. Universidad No. 1001, Col. Chamilpa, 62010 Cuernavaca, Morelos Mexico., Valadez-Graham V; 4Biotechnology Institute, National Autonomous University of México, Av. Universidad 2001, Col. Chamilpa, 62210 Cuernavaca, Morelos Mexico., Deas J; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Gómez-Cerón C; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Tavira-Montalván CA; 3Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Autonomous University of Morelos State, Av. Universidad No. 1001, Col. Chamilpa, 62010 Cuernavaca, Morelos Mexico., Arizmendi-Heras A; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Ramírez-Bello J; 5Endocrine and Metabolic Disease Unit Research, Hospital Juárez of México, Av. Instituto Politécnico Nacional 5160, Col. Magdalena de las Salinas, 07760 Ciudad de México, Mexico., Zurita-Ortega ME; 4Biotechnology Institute, National Autonomous University of México, Av. Universidad 2001, Col. Chamilpa, 62210 Cuernavaca, Morelos Mexico., Illades-Aguiar B; Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Av. Lázaro Cárdenas S/N, Col. Haciendita, 39070 Chilpancingo, Guerrero Mexico., Leyva-Vázquez MA; Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Av. Lázaro Cárdenas S/N, Col. Haciendita, 39070 Chilpancingo, Guerrero Mexico., Fernández-Tilapa G; Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Av. Lázaro Cárdenas S/N, Col. Haciendita, 39070 Chilpancingo, Guerrero Mexico., Bermúdez-Morales VH; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Madrid-Marina V; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico., Rodríguez-Dorantes M; 6National Institute of Genomic Medicine, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Ciudad de México, Mexico., Pérez-Plasencia C; 7Oncogenomics Laboratory, National Cancer Institute of Mexico, Av. San Fernando No. 22, Col. Sección XVI, 14080 Ciudad de México, Mexico.; Biomedicine Unit, FES-Iztacala UNAM, Av. De los Barrios S/N. Col. Los Reyes Iztacala, 54090 Tlalnepantla de Baz, Estado de México Mexico., Peralta-Zaragoza O; 2Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera. Col. Santa María Ahuacatitlán, 62100 Cuernavaca, Morelos Mexico.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2019 Aug 15; Vol. 19, pp. 214. Date of Electronic Publication: 2019 Aug 15 (Print Publication: 2019).
DOI: 10.1186/s12935-019-0931-x
Abstrakt: 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.
Competing Interests: Competing interestsThe authors declare that they have no competing interests.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje