IGFBP7-AS1 is a p53-responsive long noncoding RNA downregulated by Epstein-Barr virus that contributes to viral tumorigenesis.

Abstract

Epstein-Barr virus (EBV) is closely related to the development of several malignancies, such as B-cell lymphoma (B-CL), by the mechanism through which these malignancies develop remains largely unknown. We previously observed downregulation of the long noncoding RNA (lncRNA) IGFBP7-AS1 in response to EBV infection. However, the role of IGFBP7-AS1 in EBV-associated cancers has not been clarified. Here, we found that expression of IGFBP7-AS1, as well as its sense gene IGFBP7, is decreased in EBV-positive B-CL cells and clinical tissues. IGFBP7-AS1 stabilizes IGFBP7 mRNA by forming a duplex based on their overlapping regions. The tumour suppressor p53 transcriptionally activates IGFBP7-AS1 expression by binding to the promoter region of the lncRNA gene. The IGFBP7-AS1 expression is able to be rescued in EBV-positive cells in wild-type (wt) p53-dependent manner. IGFBP7-AS1 inhibits the proliferation and promotes the apoptosis of B-CL cells. Moreover, tumorigenic properties due to the depletion of IGFBP7-AS1 were restored by exogenous expression of IGFBP7 or wt-p53. Furthermore, the functional p53/IGFBP7-AS1/IGFBP7 axis facilitates apoptosis by suppressing the production and secretion of the NPPB signal peptide and further regulating the cGMP-PKG signalling pathway. This study demonstrates that EBV promotes tumorigenesis, particularly in B-CL progression, by downregulating the novel p53-responsive lncRNA IGFBP7-AS1.

• Authors: Wei Dang, Pengfei Cao, Qijia Yan, Li Yang, Yiwei Wang, Jing Yang, Shuyu Xin, Jing Zhang, Jing Li, Sijing Long, Wentao Zhang, Senmiao Zhang, Jianhong Lu
• Journal: Cancer letters (Cancer Lett) Vol. 523 Pg. 135-147 (12 28 2021) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 34634383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Insulin-Like Growth Factor Binding Proteins
• RNA, Long Noncoding
• TP53 protein, human
• Tumor Suppressor Protein p53
• insulin-like growth factor binding protein-related protein 1
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP

Topics

• Animals
• Apoptosis
• Carcinogenesis
• Cell Line, Tumor
• Cyclic GMP (physiology)
• Cyclic GMP-Dependent Protein Kinases (physiology)
• Down-Regulation
• Epstein-Barr Virus Infections (complications)
• Female
• Herpesvirus 4, Human (pathogenicity)
• Humans
• Insulin-Like Growth Factor Binding Proteins (genetics)
• Lymphoma, B-Cell (etiology, pathology, virology)
• Mice, Inbred BALB C
• RNA, Long Noncoding (physiology)
• Tumor Suppressor Protein p53 (physiology)
• Mice