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DOI10.1073/PNAS.2014195118
Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1
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.
发表日期2021
ISSN00278424
卷号118期号:3
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Human papillomavirus; LncRNA; Oncoproteins; Transcription; YY1
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181014
作者单位Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States; Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China; Genome Technology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States; Stomatological Hospital of Tianjin Medical University, Tianjin, 300070, China; Amsterdam Universitair Medische Centra, Pathology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, Netherlands; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033, United States
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Liu H.,Xu J.,Yang Y.,et al. Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1[J],2021,118(3).
APA Liu H..,Xu J..,Yang Y..,Wang X..,Wu E..,...&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,118(3).
MLA Liu H.,et al."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 118.3(2021).
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