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

Autor:	Liu H; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702., Xu J; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.; Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China., Yang Y; Genome Technology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892., Wang X; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702., Wu E; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702., Majerciak V; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702., Zhang T; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.; Stomatological Hospital of Tianjin Medical University, Tianjin 300070, China., Steenbergen RDM; Amsterdam Universitair Medische Centra, Pathology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Wang HK; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294., Banerjee NS; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294., Li Y; Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China., Lu W; Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China., Meyers C; Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033., Zhu J; Genome Technology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892., Xie X; Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China., Chow LT; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294; ltchow@uab.edu zhengt@exchange.nih.gov., Zheng ZM; Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702; ltchow@uab.edu zhengt@exchange.nih.gov.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Jan 19; Vol. 118 (3).
DOI:	10.1073/pnas.2014195118
Abstrakt:	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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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