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.

中文翻译：

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HPV16感染调节p53介导的RASSF1A转录。

人乳头瘤病毒（HPV）16感染和RASSF1A表达在肿瘤的发生和发展中起重要作用。然而，它们在生殖系统肿瘤的发展中协调一致的功能所依据的确切机制仍有待阐明。在本研究中，我们显示HPV16-E6通过降解p53选择性上调RASSF1A表达，p53与RASSF1A启动子相互作用并调节细胞凋亡。p53的过度表达触发了SiHa细胞中内源性RASSF1A的减少，并伴有细胞凋亡。同样，在具有RNA干扰（RNAi）的SiHa细胞中内源性HPV16-E6的敲低导致p53介导的RASSF1A的下调和随后的凋亡诱导。这些发现共同表明，HPV16感染调节p53介导的RASSF1A表达并抑制细胞凋亡。此外，RASSF1A可能形成负的自动调节反馈回路的一个因素，该回路作用于HPV16应答并参与p53依赖性细胞凋亡。我们的结果为肿瘤发展的细胞机制提供了新的见解，并为癌症治疗和有效诊断中新策略的发展提供了起点。