The Long Noncoding RNA MEG3 Contributes to Cisplatin Resistance of Human Lung Adenocarcinoma.
The Long Noncoding RNA MEG3 Contributes to Cisplatin Resistance of Human Lung Adenocarcinoma.
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长非编码 RNA MEG3 有助于人肺腺癌的顺铂耐药性。
DOI：
10.1371/journal.pone.0114586
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Liu J;Wan L;Lu K;Sun M;Pan X;Zhang P;Lu B;Liu G;Wang Z
长链非编码RNA（longnoncodingRNA，lncRNA）是一类与肿瘤发生和化疗耐药有关的癌基因或抑癌基因。母系表达基因3（MEG 3）是位于14 q32的印迹基因，其编码lncRNA，并且MEG 3表达降低在多种癌症中起重要作用。然而，其在人肺腺癌（LAD）化疗耐药表型发展中的生物学作用尚不清楚。本研究旨在观察MEG 3在LAD中的表达，探讨MEG 3在LAD顺铂耐药中的生物学作用及临床意义。lncRNA微阵列显示，顺铂耐药A549/DDP细胞中MEG 3的表达明显低于亲本A549细胞。MEG 3在A549/DDP细胞中的过表达通过抑制细胞增殖和诱导细胞凋亡来增加其在体外和体内对顺铂的化疗敏感性。相反，在A549细胞中MEG 3敲低降低了化疗敏感性。此外，MEG 3在顺铂不敏感的LAD组织中减少，而p53蛋白水平降低，Bcl-xl蛋白水平升高。此外，MEG 3表达水平较低的患者对顺铂化疗的反应较差。这些发现表明，MEG 3在LAD中显著下调，并通过控制p53和Bcl-xl表达部分调节LAD细胞的顺铂抗性。因此，MEG 3可能代表顺铂反应不良的新标志物，并可能成为LAD化疗的潜在治疗靶点。
Long noncoding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors that are involved in tumorigenesis and chemotherapy drug resistance. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes an lncRNA, and decreased MEG3 expression plays an important role in multiple cancers. However, its biological role in the development of the chemoresistance phenotype of human lung adenocarcinoma (LAD) is unknown. This study aimed to observe the expression of MEG3 in LAD and to evaluate its biological role and clinical significance in the resistance of LAD cells to cisplatin. MEG3 expression was markedly decreased in cisplatin-resistant A549/DDP cells compared with parental A549 cells as shown by an lncRNA microarray. MEG3 overexpression in A549/DDP cells increased their chemosensitivity to cisplatin both in vitro and in vivo by inhibiting cell proliferation and inducing apoptosis. By contrast, MEG3 knockdown in A549 cells decreased the chemosensitivity. Moreover, MEG3 was decreased in cisplatin-insensitive LAD tissues while p53 protein levels were decreased and Bcl-xl protein levels increased. Furthermore, patients with lower levels of MEG3 expression showed worse responses to cisplatin-based chemotherapy. These findings demonstrate that MEG3 is significantly downregulated in LAD and partially regulates the cisplatin resistance of LAD cells through the control of p53 and Bcl-xl expression. Thus, MEG3 may represent a new marker of poor response to cisplatin and could be a potential therapeutic target for LAD chemotherapy.
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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。
影响因子：
3.8
作者：
Lu KH;Li W;Liu XH;Sun M;Zhang ML;Wu WQ;Xie WP;Hou YY
通讯作者：
Hou YY
影响因子：
4.8
作者：
Tomita, Y;Marchenko, N;Moll, UM
通讯作者：
Moll, UM
影响因子：
3.1
作者：
Walia, Vijay;Kakar, Smita;Elble, Randolph
通讯作者：
Elble, Randolph
影响因子：
37.3
作者：
Gibb EA;Brown CJ;Lam WL
通讯作者：
Lam WL
影响因子：
8
作者：
Al-Bahlani, S.;Fraser, M.;Wong, A. Y. C.;Sayan, B. S.;Bergeron, R.;Melino, G.;Tsang, B. K.
通讯作者：
Tsang, B. K.