Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression.
Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression.
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长链非编码RNA MEG3通过影响p53表达抑制NSCLC细胞增殖并诱导细胞凋亡。
DOI：
10.1186/1471-2407-13-461
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发表时间：
2013-10-07
期刊：
影响因子：
3.8
通讯作者：
Hou YY
中科院分区：
文献类型：
--
作者：
Lu KH;Li W;Liu XH;Sun M;Zhang ML;Wu WQ;Xie WP;Hou YY
长链非编码RNA在肿瘤发生中起着重要作用，因此，鉴定肿瘤相关lncRNA并研究其生物学功能和分子机制对于了解肿瘤的发生和发展具有重要意义。最近，在多种人类癌症中观察到lncRNA MEG 3的下调。然而，其在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究的目的是检测MEG 3在NSCLC中的表达模式，并评估其在肿瘤进展中的生物学作用和临床意义。通过qRT-PCR分析MEG 3在44个NSCLC组织和7个NSCLC细胞系中的表达。采用过表达方法研究MEG 3在NSCLC细胞中的生物学功能。亚硫酸氢盐测序用于研究MEG 3表达的DNA甲基化。MTT法和集落形成实验检测MEG 3对细胞增殖的影响，Hoechst染色和流式细胞仪检测MEG 3对细胞凋亡的影响。将转染pCDNA-MEG 3的NSCLC细胞注射到裸鼠体内，以研究MEG 3对体内成瘤的影响。通过蛋白质印迹分析测定MEG 3靶标的蛋白质水平。使用Student t检验（双尾）检验组间差异的显著性。MEG 3在非小细胞肺癌（NSCLC）肿瘤组织中的表达低于正常组织，且与晚期病理分期和肿瘤大小相关。此外，MEG 3表达水平较低的患者预后相对较差。MEG 3的过表达在体外可抑制NSCLC细胞的增殖，诱导细胞凋亡，在体内可抑制肿瘤的发生。MEG 3在体外过表达可影响MDM 2和p53蛋白水平。我们的研究结果表明，MEG 3在NSCLC组织中显著下调，可能受到DNA甲基化的影响，并调节NSCLC细胞的增殖和凋亡，部分通过激活p53。因此，MEG 3可能代表一种新的预后不良的标志物，是NSCLC干预的潜在治疗靶点。
Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
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影响因子：
8
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
通讯作者：
Patel, T.
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Khaitan, Divya;Dinger, Marcel E.;Perera, Ranjan J.
通讯作者：
Perera, Ranjan J.
影响因子：
4
作者：
Wang, Pengjun;Ren, Zhongqiao;Sun, Piyun
通讯作者：
Sun, Piyun