title: HPV16 infection regulates RASSF1A transcription mediated by p53.
abstract: Human papillomavirus (HPV) 16 infection and RASSF1A expression play important roles in tumor development and progression. However, the precise mechanisms underlying their concerted function in the development of reproductive system tumors still remain to be elucidated. In the present study, we showed that HPV16-E6 selectively upregulates RASSF1A expression via degradation of p53, which interacts with the RASSF1A promoter and regulates apoptosis. Overexpression of p53 triggered a decrease in endogenous RASSF1A in SiHa cells, accompanied by apoptosis. Similarly, knockdown of endogenous HPV16-E6 in SiHa cells with RNA interference (RNAi) led to downregulation of RASSF1A mediated by p53 and the subsequent induction of apoptosis. These findings collectively suggest that HPV16 infection regulates p53-mediated RASSF1A expression and suppresses apoptosis. Moreover, RASSF1A may form an element of the negative autoregulatory feedback loops that act on the HPV16 response and are involved in p53-dependent apoptosis. Our results provide novel insights into the cellular mechanism of tumor development, and present a starting point for the development of novel strategies in cancer treatment and effective diagnosis.
authors.affiliation: Department of Anatomy and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yueshan
authors.initials: Y
authors.lastname: Lei
authors.forename: Chengjun
authors.initials: C
authors.lastname: Hu
authors.forename: Hongxin
authors.initials: H
authors.lastname: Xu
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tian
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C411762:RASSF1 protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins