Biochemistry Program, Sackler School of Graduate Biomedical Sciences and Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, United States.
Biochemistry Program, Sackler School of Graduate Biomedical Sciences and Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, United States.
Virology. 2018 May;518:8-13. doi: 10.1016/j.virol.2018.01.031. Epub 2018 Feb 7.
Modulation of expression of noncoding RNAs is an important aspect of the oncogenic activities of high-risk human papillomavirus (HPV) E6 and E7 proteins. While HPV E6/E7-mediated alterations of microRNAs (miRNAs) has been studied in detail there are fewer reports on HPV-mediated dysregulation of long noncoding RNAs (lncRNAs). The cervical carcinoma expressed PCNA regulatory (CCEPR) lncRNA is highly expressed in cervical cancers and expression correlates with tumor size and patient outcome. We report that CCEPR is a nuclear lncRNA and that HPV16 E6 oncogene expression causes increased CCEPR expression through a mechanism that is not directly dependent on TP53 inactivation. CCEPR depletion in cervical carcinoma cell lines reduces viability, while overexpression enhances viability. In contrast to what was published and inspired its designation, there is no evidence for PCNA mRNA stabilization, and hence CCEPR likely functions through a different mechanism.
非编码 RNA 的表达调控是高危型人乳头瘤病毒（HPV）E6 和 E7 蛋白致癌活性的一个重要方面。虽然 HPV E6/E7 介导的 microRNAs（miRNAs）改变已经得到了详细研究，但关于 HPV 介导的长非编码 RNA（lncRNA）失调的报道较少。宫颈癌细胞表达的 PCNA 调控（CCEPR）lncRNA 在宫颈癌中高度表达，其表达与肿瘤大小和患者预后相关。我们报告 CCEPR 是一种核 lncRNA，HPV16 E6 癌基因表达通过一种不直接依赖于 TP53 失活的机制导致 CCEPR 表达增加。在宫颈癌细胞系中耗尽 CCEPR 会降低细胞活力，而过表达则会增强细胞活力。与已发表的并启发其命名的内容相反，没有证据表明 PCNA mRNA 稳定，因此 CCEPR 可能通过不同的机制发挥作用。
