Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1

• DOI: 10.1073/pnas.2014195118
• Publication Date: 2021-01-12T22:41:35Z
• Authors: Haibin Liu; Junfen Xu; Yanqin Yang; Xiaohong Wang; Ethan Wu; Vladimir Majerciak; Tingting Zhang; Renske D. M. Stee...; Hsu-Kun Wang; Nilam S. Banerjee; Yang Li; Weiguo Lu; Craig Meyers; Jun Zhu; Xing Xie; Louise T. Chow; Zhi-Ming Zheng
• Keywords: Keratinocytes; 0301 basic medicine; Human papillomavirus 16; Base Sequence; Human papillomavirus 18; Carcinogenesis; Papillomavirus E7 Proteins; Papillomavirus Infections; Cervix Uteri; Retinoblastoma Protein; Fanconi Anemia Complementation Group Proteins; E2F Transcription Factors; 3. Good health; Alternative Splicing; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Cell Line, Tumor; Host-Pathogen Interactions; Humans; Female; RNA, Long Noncoding; Promoter Regions, Genetic

Significance

Persistent infections of oncogenic HPVs can lead to cervical, anogenital, and head-and-neck cancers. We report that HPV-infected cervical lesions display aberrant expression of 194 long-noncoding RNAs, including lnc-FANCI-2 . We show that, in cell and tissue cultures, lnc-FANCI-2 is induced primarily by the oncogenic HPV E7 protein via interacting with a cellular transcription factor YY1. HPV infection also increases YY1 protein expression by reducing miR-29a, which targets the 3′ UTR of YY1 RNA. In vivo and in vitro, the nearby DNA repair gene FANCI is co-upregulated. These findings highlight an aspect on how oncogenic HPV E7 contributes to pathogenesis.