The long non-coding RNA maternally expressed gene 3 activates p53 and is downregulated in esophageal squamous cell cancer
The long non-coding RNA maternally expressed gene 3 activates p53 and is downregulated in esophageal squamous cell cancer
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DOI：
10.1007/s13277-016-5426-y
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发表时间：
2016-12-01
期刊：
影响因子：
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通讯作者：
Zhang, Xuefei
中科院分区：
文献类型：
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作者：
Lv, Desheng;Sun, Run;Zhang, Xuefei
食道鳞状细胞癌(ESCC)是一种恶性侵袭性疾病，存活率低。长非编码RNA(Long Non-Coding RNAs，LncRNAs)在肿瘤的发生、发展中起重要作用，因此，LncRNAs也参与食管癌的发生发展。本研究采用实时定量聚合酶链式反应(qRT-PCR)技术，对食管鳞癌组织中母体表达基因3(MEG3)的表达进行了研究。在ESCC细胞系中进行MEG3的异位表达。异位表达MEG3后，分析细胞的增殖和凋亡情况。我们通过qRT-PCR发现MEG3在ESCC组织中的表达明显低于正常组织。MEG3的低表达与食管鳞癌患者的淋巴结转移和分期有关，并提示患者的生存期较短(HR=0.471，95%CI 0.234~0.950，P=0.035)，这一结果得到了食管癌基因组图谱数据的证实。DNA去甲基化药物5-氮杂-2-脱氧胞苷(5-aza-2-deoxy-cytidine，5-aza-CDR)处理后，食管癌细胞MEG3的表达水平显著升高，TCGA食道癌数据也显示MEG3的DNA甲基化预示着生存。MEG3在ESCC细胞中的异位表达抑制了细胞的增殖，促进了细胞的凋亡，抑制了转移。进一步的研究表明，MEG3通过下调小鼠双分钟2同源基因(MDM2)激活P53及其靶基因的表达。总之，我们的研究表明MEG3在ESCC中的表达缺失是常见的，MEG3可以激活P53并预测ESCC的预后。
Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor survival. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression; hence, lncRNAs are also involved in the development and progression of ESCC. In this study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression of lncRNA, maternally expressed gene 3 (MEG3) in ESCC. Ectopic expression of MEG3 was performed in ESCC cell lines. Proliferation and apoptosis of ESCC cell lines were analyzed after ectopic expression of MEG3. We found MEG3 was significantly downregulated in ESCC tissues compared with normal tissues by qRT-PCR. Low expression of MEG3 was correlated with lymph node metastasis and advanced TNM stages of ESCC patients and indicated shorter survival (HR = 0.471, 95% CI 0.234-0.950, P = 0.035), which was confirmed by The Cancer Genome Atlas (TCGA) esophageal cancer dataset. DNA-demethylating agent (5-aza-2-deoxy-cytidine (5-aza-CdR)) treatment significantly increased MEG3 expression level in ESCC cells, and TCGA esophageal cancer dataset also showed that DNA methylation of MEG3 predicted survival. Ectopic expression of MEG3 in ESCC cells inhibited cell proliferation, promoted apoptosis, and suppressed metastasis. Further investigation showed enforced expression of MEG3 activated p53 and its target genes by downregulation of mouse double minute 2 homolog (MDM2). Overall, our study indicated that MEG3 expression loss is common in ESCC and MEG3 could activate p53 and predict prognosis in ESCC.