microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.
microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.
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微小RNA - 29可调控肝细胞癌中长链非编码RNA基因MEG3的表达。
DOI：
10.1038/onc.2011.193
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发表时间：
2011-11-24
期刊：
影响因子：
8
通讯作者：
Patel, T.
中科院分区：
文献类型：
--
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
人类基因组中充满了长的非编码RNA(LncRNA)，其中许多是转录的，可能具有功能作用。对23000个LncRNA的芯片分析显示，712个(~3%)LncRNA在恶性肝细胞中表达下调，其中母系表达基因3(MEG3)相对于非恶性肝细胞的表达下调了210倍。实时荧光定量聚合酶链式反应显示，MEG3在四种人肝细胞系中的表达明显低于正常肝细胞。RNA原位杂交显示MEG3在非肿瘤性肝组织胞浆中表达较强，而在肝细胞癌组织中无表达或表达很弱。MEG3在肝癌细胞中的强制表达显著抑制了锚定依赖和非依赖的细胞生长，并诱导了细胞凋亡。甲基化特异的聚合酶链式反应检测到MEG3启动子的高甲基化，并且在5-氮-2-脱氧胞苷或siRNA对DNA甲基转移酶(DNMT)1和3b甲基化的抑制下，MEG3的表达增加。通过评估miR-29对DNMT 1和3的调节作用，研究了miRNA对MEG3表达的调节作用。mir-29a的过表达增加了MEG3的表达。与野生型对照相比，肝细胞特异性miR-29a/b1基因敲除小鼠的肝组织中MEG3的小鼠同源基因GTL2减少。这些数据表明，miR-29a对lncRNA MEG3的甲基化依赖的组织特异性调控可能有助于肝癌的生长，并突显了两类非编码RNA miRNAs和lncRNAs之间的相互关系，以及基因表达的表观遗传调控。
The human genome is replete with long non-coding RNAs (lncRNA), many of which are transcribed and likely to have a functional role. Microarray analysis of > 23 000 lncRNAs revealed downregulation of 712 (~3%) lncRNA in malignant hepatocytes, among which maternally expressed gene 3 (MEG3) was downregulated by 210-fold relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. RNA in situ hybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. MEG3 promoter hypermethylation was identified by methylation-specific PCR and MEG3 expression was increased with inhibition of methylation with either 5-Aza-2-Deoxycytidine, or siRNA to DNA Methyltransferase (DNMT) 1 and 3b in HCC cells. MiRNA-dependent regulation of MEG3 expression was studied by evaluating the involvement of miR-29, which can modulate DNMT 1 and 3. Overexpression of mir-29a increased expression of MEG3. GTL2, the murine homolog of MEG3, was reduced in liver tissues from hepatocyte-specific miR-29a/b1 knock-out mice compared with wild-type controls. These data show that methylation-dependent tissue-specific regulation of the lncRNA MEG3 by miR-29a may contribute to HCC growth and highlight the inter-relationship between two classes of non-coding RNA, miRNAs and lncRNAs, and epigenetic regulation of gene expression.
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影响因子：
13.5
作者：
Wang, Bo;Majumder, Sarmila;Nuovo, Gerard;Kutay, Huban;Volinia, Stefano;Patel, Tushar;Schmittgen, Thomas D.;Croce, Carlo;Ghoshal, Kalpana;Jacob, Samson T.
通讯作者：
Jacob, Samson T.
影响因子：
8
作者：
Lujambio, A.;Portela, A.;Liz, J.;Melo, S. A.;Rossi, S.;Spizzo, R.;Croce, C. M.;Calin, G. A.;Esteller, M.
通讯作者：
Esteller, M.
DOI：
10.3816/clm.2008.n.021
发表时间：
2008-06-01
期刊：
CLINICAL LYMPHOMA & MYELOMA
影响因子：
--
作者：
Benetatos, Leonidas;Dasoula, Aggeliki;Bourantas, Konstantinos L.
通讯作者：
Bourantas, Konstantinos L.
影响因子：
25.7
作者：
Cazals-Hatem, D;Rebouissou, S;Zucman-Rossi, J
通讯作者：
Zucman-Rossi, J
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW