Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer

Abstract

BackgroundOur previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed to further elucidate the role and potential inactivation mechanism of MEG3 in cervical cancer.MethodsROC curve and Cox regression analyses were used to assess the diagnostic and prognostic value of MEG3 in patients with cervical cancer. The methylation status of the MEG3 promoter in cervical cancer tissue samples was tested using methylation-specific PCR. Furthermore, we altered the methylation status of the MEG3 promoter in two cervical cancer cell lines (HeLa and CaSki) using a DNA methylation transfer enzyme inhibitor (5-Aza-CdR), to investigate whether promoter hypermethylation is a potential cause of MEG3 inactivation. Finally, we used CCK-8 and colony formation assays to evaluate the cell proliferation ability of HeLa and CaSki cells that had been treated with 5-aza-CdR, to investigate whether downregulation of MEG3 caused by promoter hypermethylation had biological effects.ResultsROC curve analysis indicated that MEG3 status showed sufficient sensitivity and specificity for prediction of tumor size and lymph node metastasis in patients with cervical cancer. In addition, our follow-up data showed that low MEG3 expression was correlated with recurrence and short overall survival. Moreover, hypermethylation of the MEG3 promoter was observed in most cervical cancer tissue samples, and demethylation of the MEG3 promoter led to re-expression of MEG3 and inhibited proliferation of HeLa and CaSki cells.Conclusions MEG3 is a powerful tool for diagnosis and prognosis of patients with cervical cancer, and low expression of MEG3 is likely to be related to promoter hypermethylation in cervical cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0472-2) contains supplementary material, which is available to authorized users.

Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

“…Aberrant DNA methylation, which is the most common epigenetic change in human malignancies, may be used as a diagnosis, surveillance and prognostic biomarker according to recent studies 14–16 . Although plasma DNA methylation has been proved to be a potential biomarker for some diseases, the study forced on DNA methylation of cancer patients’ plasma is still limited 17, 18 .…”

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…In addition, they are being identified and characterized for serial steps of cancer development, including tumor initiation, growth, and metastasis [6]. Maternally expressed gene 3 (MEG3), a lncRNA that has attracted much research interest, is aberrantly expressed in several human cancers including ovarian cancer [7], gastric cancer [8], colorectal cancer [9], cervical cancer [10], and malignant glioma [11]. Moreover, according to these previous studies, MEG3 exhibited anti-cancer effects via regulation of cell proliferation, apoptosis, and metastasis.…”

MEG3 long non-coding RNA prevents cell growth and metastasis of osteosarcoma

“…LncRNA MEG3, which is considered as a tumor suppressor gene, is well studied in a variety of caners (20). MEG3 was down-regulated in cervical cancer, and is a potential marker for diagnosis and prognosis of patients with cervical cancer (21). Ectopic expression of MEG3 in nasopharyngeal carcinoma cells could inhibit cell proliferation, colony formation and induce cell cycle arrest (22).…”