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DOI | 10.1073/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 |
ISSN | 00278424 |
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
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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 |
推荐引用方式 GB/T 7714 | 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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