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Downregulation of long non‐coding RNA MEG3 in nasopharyngeal carcinoma
Author(s) -
Chak WingPo,
Lung Raymond WaiMing,
Tong Joanna HungMan,
Chan Sylvia YatYee,
Lun Samantha WeiMan,
Tsao SaiWah,
Lo KwokWai,
To KaFai
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22569
Subject(s) - meg3 , biology , downregulation and upregulation , nasopharyngeal carcinoma , cancer research , long non coding rna , ectopic expression , dna methylation , microbiology and biotechnology , rna , gene expression , cell culture , gene , genetics , medicine , radiation therapy
In our previous whole‐transcriptome sequencing analysis, downregulation of a long non‐coding RNA, maternally expressed gene 3 ( MEG3 ), was identified in NPC samples. This finding suggests the possible role of MEG3 as a tumor suppressor in this distinctive disease. In the present study, two MEG3 variants, AF119863 (MEG3‐AF) and BX247998 (MEG3‐BX) , were found abundantly expressed in a normal nasopharyngeal epithelial cell line, NP69. Significant downregulation of MEG3‐AF was further verified in a panel of NPC samples including xenografts and primary biopsies. MEG3 is an imprinted gene located within chromosome 14q32, a common deleted region in NPC. Both DNA copy number loss and aberrant promoter methylation contributed to MEG3 inactivation. Interestingly, MEG3 expression could successfully be rescued by the treatment of a demethylation agent. Besides, ectopic expression of MEG3 in NPC cell lines resulted in considerable repression of in vitro anchorage‐independent growth and in vivo tumorigenicity, in addition to significant inhibition in cell proliferation, colony formation, and induction of cell cycle arrest. Finally, we revealed the association between MEG3 activity and the p53 signaling cascade. Our findings characterize MEG3 as a tumor suppressive long non‐coding RNA in NPC and encourage the development of precise long non‐coding RNA‐targeted epigenetic therapy against this malignancy. © 2016 Wiley Periodicals, Inc.