Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer
Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer
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长链非编码RNA MEG3下调与胃癌预后不良相关并促进细胞增殖
DOI：
10.1007/s13277-013-1142-z
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发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Liu, Xianghua
中科院分区：
文献类型：
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作者：
Sun, Ming;Xia, Rui;Liu, Xianghua
长链非编码rna （lncRNAs）最近在控制基本生物学过程中发挥了重要作用，其中许多lncRNAs在表达上发生改变，可能在肿瘤发生中发挥功能作用。母系表达基因3 （MEG3）是一个位于14q32的印迹基因，编码与多种人类癌症相关的lncRNA。然而，其在胃癌发生发展中的生物学作用和临床意义尚不清楚。本研究通过定量反转录聚合酶链反应研究lncRNA MEG3在胃癌中的表达。我们发现胃癌组织中MEG3水平与邻近正常组织相比明显降低。其表达水平与TNM分期、浸润深度、肿瘤大小有显著相关性。此外，MEG3表达水平低的患者预后相对较差。此外，通过siRNA敲低MEG3表达可促进细胞增殖，而MEG3异位表达可抑制细胞增殖，促进细胞凋亡，并调节胃癌细胞系p53表达。通过5-aza-CdR处理，我们还观察到MEG3的表达可以通过DNA甲基化来调节。我们的研究结果表明，MEG3的低表达可以作为胃癌预后不良的生物标志物，并在体外调节细胞增殖和凋亡。
Long noncoding RNAs (lncRNAs) have emerged recently as major players in governing fundamental biological processes, and many of which are altered in expression and likely to have a functional role in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA associated with various human cancers. However, its biological role and clinical significance in gastric cancer development and progression are unknown. In this study, to investigate the lncRNA MEG3 expression in gastric cancer, quantitative reverse-transcription polymerase chain reaction was conducted. We found that MEG3 levels were markedly decreased in gastric cancer tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, depth of invasion, and tumor size. Moreover, patients with low levels of MEG3 expression had a relatively poor prognosis. Furthermore, knockdown of MEG3 expression by siRNA could promote cell proliferation, while ectopic expression of MEG3 inhibited cell proliferation, promoted cell apoptosis, and modulated p53 expression in gastric cancer cell lines. By 5-aza-CdR treatment, we also observed that MEG3 expression can be modulated by DNA methylation. Our findings present that MEG3 downexpression can be identified as a poor prognostic biomarker in gastric cancer and regulate cell proliferation and apoptosis in vitro.