Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1
| Autor: | Vladimir Majerciak, Xiaohong Wang, Haibin Liu, Ethan Wu, Nilam Sanjib Banerjee, Hsu Kun Wang, Junfen Xu, Renske D.M. Steenbergen, Louise T. Chow, Jun Zhu, Craig Meyers, Weiguo Lu, Yang Li, Xing Xie, Yanqin Yang, Tingting Zhang, Zhi-Ming Zheng |
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| Přispěvatelé: | CCA - Cancer biology and immunology, Pathology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
Untranslated region Polyadenylation Carcinogenesis Papillomavirus E7 Proteins Ubiquitin-Protein Ligases Uterine Cervical Neoplasms Cervix Uteri Biology Retinoblastoma Protein Transcription (biology) Cell Line Tumor Humans Promoter Regions Genetic E2F Gene YY1 Transcription Factor Human papillomavirus 16 Multidisciplinary Base Sequence Human papillomavirus 18 Papillomavirus Infections Promoter Biological Sciences Fanconi Anemia Complementation Group Proteins Long non-coding RNA E2F Transcription Factors Cell biology Alternative Splicing MicroRNAs Gene Expression Regulation FANCI Gene Host-Pathogen Interactions Female RNA Long Noncoding Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 118(3):e2014195118. National Academy of Sciences Proc Natl Acad Sci U S A Liu, H, Xu, J, Yang, Y, Wang, X, Wu, E, Majerciak, V, Zhang, T, Steenbergen, R D M, Wang, H-K, Banerjee, N S, Li, Y, Lu, W, Meyers, C, Zhu, J, Xie, X, Chow, L T & Zheng, Z-M 2021, ' Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1 ', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 3, e2014195118 . https://doi.org/10.1073/PNAS.2014195118 |
| ISSN: | 0027-8424 |
| DOI: | 10.1073/PNAS.2014195118 |
| Popis: | Long noncoding RNAs (lncRNAs) play diverse roles in biological processes, but their expression profiles and functions in cervical carcinogenesis remain unknown. By RNA-sequencing (RNA-seq) analyses of 18 clinical specimens and selective validation by RT-qPCR analyses of 72 clinical samples, we provide evidence that, relative to normal cervical tissues, 194 lncRNAs are differentially regulated in high-risk (HR)-HPV infection along with cervical lesion progression. One such lncRNA, lnc-FANCI-2, is extensively characterized because it is expressed from a genomic locus adjacent to the FANCI gene encoding an important DNA repair factor. Both genes are up-regulated in HPV lesions and in in vitro model systems of HR-HPV18 infection. We observe a moderate reciprocal regulation of lnc-FANCI-2 and FANCI in cervical cancer CaSki cells. In these cells, lnc-FANCI-2 is transcribed from two alternative promoters, alternatively spliced, and polyadenylated at one of two alternative poly(A) sites. About 10 copies of lnc-FANCI-2 per cell are detected preferentially in the cytoplasm. Mechanistically, HR-HPVs, but not low-risk (LR)-HPV oncogenes induce lnc-FANCI-2 in primary and immortalized human keratinocytes. The induction is mediated primarily by E7, and to a lesser extent by E6, mostly independent of p53/E6AP and pRb/E2F. We show that YY1 interacts with an E7 CR3 core motif and transactivates the promoter of lnc-FANCI-2 by binding to two critical YY1-binding motifs. Moreover, HPV18 increases YY1 expression by reducing miR-29a, which targets the 3' untranslated region of YY1 mRNA. These data have provided insights into the mechanisms of how HR-HPV infections contribute to cervical carcinogenesis. |
| Databáze: | OpenAIRE |
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