1. IGFBP7-AS1 is a p53-responsive long noncoding RNA downregulated by Epstein-Barr virus that contributes to viral tumorigenesis.
- Author
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Dang, Wei, Cao, Pengfei, Yan, Qijia, Yang, Li, Wang, Yiwei, Yang, Jing, Xin, Shuyu, Zhang, Jing, Li, Jing, Long, Sijing, Zhang, Wentao, Zhang, Senmiao, and Lu, Jianhong
- Subjects
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LINCRNA , *EPSTEIN-Barr virus , *CELLULAR signal transduction , *NEOPLASTIC cell transformation , *PROMOTERS (Genetics) , *SYNCRIP protein , *RNA physiology , *PROTEINS , *BIOCHEMISTRY , *RESEARCH , *ANIMAL experimentation , *PHENOMENOLOGICAL biology , *CARCINOGENESIS , *RESEARCH methodology , *B cell lymphoma , *APOPTOSIS , *EVALUATION research , *NUCLEOTIDES , *COMPARATIVE studies , *TRANSFERASES , *CELL lines , *EPSTEIN-Barr virus diseases , *CARRIER proteins , *MICE , *DISEASE complications - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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