Downregulation of long non-coding RNA MEG3 in nasopharyngeal carcinoma.
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.
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Wing-Po
WP
Chak
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Raymond Wai-Ming
RW
Lung
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Joanna Hung-Man
JH
Tong
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Sylvia Yat-Yee
SY
Chan
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Samantha Wei-Man
SW
Lun
Li Ka Shing Faculty of Medicine, School of Biomedical Science and Center for Cancer Research, The University of Hong Kong, HKSAR, China.
Sai-Wah
SW
Tsao
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Kwok-Wai
KW
Lo
State Key Laboratory of Oncology in South China, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, HKSAR, China.|Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.|Partner State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, HKSAR, China.
Ka-Fai
KF
To
D000818:Animals; D002277:Carcinoma / Q000235:genetics*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*
C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding
MEG3; NPC; lncRNA; promoter hypermethylation; tumor suppression