ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF.
ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF.
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ZFPM2-AS1是一种新型lncRNA，通过稳定MIF减弱p53通路并促进胃癌发生
DOI：
10.1038/s41388-018-0387-9
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发表时间：
2018-11
期刊：
影响因子：
8
通讯作者：
Xie K
中科院分区：
文献类型：
--
作者：
Kong F;Deng X;Kong X;Du Y;Li L;Zhu H;Wang Y;Xie D;Guha S;Li Z;Guan M;Xie K
长链非编码rna （lncRNAs）参与了许多癌症的发病机制。在此，我们报告了我们发现的一种新的lncRNA， ZFPM2反义RNA 1 (ZFPM2- as1)，及其在胃癌发生中的关键作用。采用Gene expression Omnibus数据集分析ZFPM2-AS1在胃癌标本中的表达，并采用qRT-PCR对73对胃肿瘤和正常邻近胃组织标本进行验证。通过改变ZFPM2-AS1在体外和体内的表达，探讨ZFPM2-AS1表达对胃癌细胞增殖和凋亡的影响。利用细胞生物学和分子生物学方法对其机理进行了研究。ZFPM2-AS1在胃肿瘤组织中的表达高于正常胃组织。胃癌标本中ZFPM2-AS1表达升高与肿瘤大小、浸润深度、分化分级、TNM分期有关。ZFPM2-AS1高表达可显著降低胃癌患者的总生存率和无病生存率。功能实验表明，ZFPM2-AS1在体外可促进胃癌细胞增殖、抑制凋亡，在体内可促进肿瘤生长。这种效应与p53的核易位减弱有关。机制实验表明，肿瘤激活的ZFPM2-AS1可以结合并保护巨噬细胞迁移抑制因子（MIF）的降解，巨噬细胞迁移抑制因子是p53的有效不稳定因子。敲低MIF表达可减弱ZFPM2-AS1对胃癌细胞中p53表达的影响。我们的研究结果表明，ZFPM2-AS1调节胃癌的进展，并揭示了一个新的ZFPM2-AS1/MIF/p53信号轴，揭示了某些恶性胃细胞致瘤性的分子机制。
Long non-coding RNAs (lncRNAs) are implicated to be involved in the pathogenesis of many cancers. Herein we report on our discovery of a novel lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), and its critical role in gastric carcinogenesis. ZFPM2-AS1 expression in gastric cancer specimens was analyzed using Gene Expression Omnibus data set and validated in 73 paired gastric tumor and normal adjacent gastric tissue specimens using qRT-PCR. The effect of ZFPM2-AS1 expression on proliferation and apoptosis in gastric cancer cells was assessed by altering its expression in vitro and in vivo. Mechanistic investigation was carried out using cell and molecular biological approaches. ZFPM2-AS1 expression was higher in gastric tumors than in normal gastric tissue. Also, increased ZFPM2-AS1 expression in gastric cancer specimens was associated with tumor size, depth of tumor invasion, differentiation grade, and TNM stage. High ZFPM2-AS1 expression predicted markedly reduced overall and disease-free survival in gastric cancer patients. Functional experiments demonstrated that ZFPM2-AS1 expression promoted proliferation and suppressed apoptosis of gastric cancer cells in vitro and promoted tumor growth in vivo. This effect is associated with attenuated nuclear translocation of p53. Mechanistic experiments demonstrated that tumor-activated ZFPM2-AS1 could bind to and protect the degradation of macrophage migration inhibitory factor (MIF), a potent destabilizer of p53. Knockdown of MIF expression diminished ZFPM2-AS1’s impact on p53 expression in gastric cancer cells. Our findings demonstrated that ZFPM2-AS1 regulates gastric cancer progression and revealed a novel ZFPM2-AS1/MIF/p53 signaling axis, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant gastric cells.
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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
巨噬细胞迁移抑制因子以p53依赖性方式激活缺氧诱导因子。
影响因子：
3.7
作者：
Oda, Seiko;Oda, Tomoyuki;Nishi, Kenichiro;Takabuchi, Satoshi;Wakamatsu, Takuhiko;Tanaka, Tomoharu;Adachi, Takehiko;Fukuda, Kazuhiko;Semenza, Gregg L.;Hirota, Kiichi
通讯作者：
Hirota, Kiichi
影响因子：
--
作者：
Bellini MF;Cadamuro AC;Succi M;Proença MA;Silva AE
通讯作者：
Silva AE
影响因子：
29.4
作者：
IMAZEKI, F;OMATA, M;ISONO, K
通讯作者：
ISONO, K
影响因子：
4.3
作者：
Lin, Yingsong;Ueda, Junko;Inoue, Manami
通讯作者：
Inoue, Manami