Expression of the cervical carcinoma expressed PCNA regulatory (CCEPR) long noncoding RNA is driven by the human papillomavirus E6 protein and modulates cell proliferation independent of PCNA

Highlights: • The HPV E6 protein drives expression of the CCEPR long noncoding RNA (lncRNA). • CCEPR induction is independent of TP53 inactivation. • CCEPR regulates cellular proliferation. • CCEPR levels do not correlate with PCNA levels. 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.