Abstract
BackgroundGene 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.MethodsTo 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.ResultsWe 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.ConclusionsOur 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.
Highlights
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
In order to clarify the status of miR-21 gene expression under activator protein 1 (AP-1) regulation in cervical tumor cells, we evaluated the expression level of miR-21 in SiHa and HaCaT cells treated with PMA and SR11302 by real-time qRTPCR and we found a heterogeneous expression of this microRNA
Our results indicate that constitutive activation of AP-1 transcription factor can induce the expression of miR-21 in human cervical cancer cells transformed with oncogenic human papillomavirus (HPV)
Summary
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. We analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells. Understanding of the complexity of tumor cells has been significantly enhanced with the discovery of genes producing small non-coding RNAs known as microRNAs. it has become evident that abnormalities in microRNA expression can contribute to carcinogenesis [1]. Most DNA binding elements and transcription factor binding sites in microRNA promoter regions are the same as those that control protein-coding genes. MicroRNAs and transcription factors can cause biological alterations in tumor cells leading to the event cascades of regulatory genetic networks and represent a challenge in the study of carcinogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
