title: Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer.
abstract: Maternally expressed 3 (MEG3) is a long non-coding RNA that can activate p53 and inhibit tumorigenesis and progression of various types of cancers. However, the role of MEG3 in epithelial ovarian cancer (EOC) is still unknown. The aim of the present study was to confirm whether MEG3 is downregulated in human EOC, determine its possible mechanism of action and elucidate the role of MEG3 in EOC. Differences in the expression of MEG3 and in the methylation status of the MEG3 promoter between EOC and normal ovary were analyzed using RT-PCR and methylation-specific PCR (MSP), respectively. MTT and EdU assays and flow cytometric analysis were used to assess the growth of ovarian cancer cells after overexpression of MEG3. The target genes regulated by MEG3 were detected with the Dual Luciferase Reporter system. The expression levels of target genes were confirmed using RT-PCR and western blotting. In contrast to normal ovarian tissues, the expression of MEG3 was absent or decreased in most EOC tissues as well as in human EOC cell lines, and the promoter of the MEG3 gene was highly methylated in both cancer tissues and cell lines. Treatment with 5-aza-2-deoxycytidine reversed the promoter hypermethylation and increased MEG3 expression. In addition, ectopic expression of MEG3 suppressed the proliferation and growth of OVCAR3 cells and promoted apoptosis. Finally, MEG3 activated p53 in OVCAR3 cells. In conclusion, our data suggest that MEG3 is epigenetically silenced in EOC due to promoter hypermethylation, which may contribute to the development of EOC.
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Jianqi
authors.initials: J
authors.lastname: Li
authors.affiliation: The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 510182, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Guangzhou Institute of Obstetrics and Gynecology, Guangzhou 510182, P.R. China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077209:Decitabine; D001374:Azacitidine