4 research outputs found
The Involvement of Epigenetic Mechanisms in HPVāInduced Cervical Cancer
Highārisk human papillomavirus (HPV) genotypes infection associates with cervical dysplasia and carcinogenesis. hrāHPV transforming potential is based on E6 and E7 viral oncoproteins actions on cellular proteins. A persistent infection with hrāHPV leads to progression from precursor lesions to invasive cervical cancer inducing changes in host genome and epigenome. Pathogenesis and development of cancer associated with both genetic and epigenetic defects alter transcriptional program. An important role for malignant transformation in HPVāinduced cervical cancer is played by epigenetic changes that occur in both viral and host genome. Furthermore, there are observations demonstrating that oncogenic viruses, once they integrated into host genome, become susceptible to epigenetic alterations made by host machinery. Epigenetic regulation of viral gene expression is an important factor in HPVāassociated disease. Gene expression control is complex and involves epigenetic changes: DNA methylation, histone modification, and nonācoding RNAs activity. Persistent infection with hrāHPV can cause viral DNA integration into host genome attracting defense mechanisms such as methylation machinery. In this chapter, we aim to review HPV infection role in chromatin modification/remodeling and the impact of HPV infection on nonācoding RNAs in cervix oncogenesis. The reversible nature of epigenetic alterations provides new opportunities in the development of therapeutic agents targeting epigenetic modification in oncogenesis
Mechanisms of Oncogene Activation
The main modifications that characterize cancer are represented by alterations in oncogenes, tumor-suppressor genes, and non-coding RNA genes. Most of these alterations are somatic and the process is a multistep one. Tumors often arise from an initial transformed cell, and after subsequent genetic alterations different cytogenetically clones lead to tumor heterogeneity