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.ConclusionsMEG3 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.
Highlights
Our previous study reported that Maternally expressed gene 3 (MEG3) is an important tumor suppressor gene that is inactivated in cervical cancer
Because MEG3 was shown to be significantly associated with tumor size and lymph node metastasis in our previous study, we conducted receiver operating characteristic (ROC) curve analysis to test its diagnostic value
The results showed that MEG3 could be a candidate to discriminate between tumors < 4 cm and tumors ≥ 4 cm, with an The areas under the ROC curve (AUC) of 0.745, a sensitivity of 56.1%, and a specificity of 80.6% at a cut-off value of 0.705 (P < 0.001, Fig. 1b)
Summary
Our previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. The diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. Studies have reported that lncRNAs regulate various biological processes such as gene expression, transcription, and. Expressed gene 3 (MEG3), a lncRNA that has attracted much research interest, is aberrantly expressed in several human cancers including gastric cancer [8, 9], colorectal cancer [10], retinoblastoma [11], and ovarian cancer [12] according to recent studies. Our previous study showed that MEG3 is associated with the progression of cervical cancer via regulation of cell proliferation and apoptosis [13]. The diagnostic and prognostic value of MEG3 for cervical cancer remains unknown
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