Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer.
Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer.
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DOI：
10.1371/journal.pone.0192264
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Safe S
中科院分区：
文献类型：
--
作者：
Cheng Y;Imanirad P;Jutooru I;Hedrick E;Jin UH;Rodrigues Hoffman A;Leal de Araujo J;Morpurgo B;Golovko A;Safe S
转移相关肺腺癌转录本-1（MALAT-1）是一种长链非编码RNA（lncRNA），是胰腺癌和其他几种肿瘤患者的一个负面预后因素。在这项研究中，我们表明，在Panc 1和其他胰腺癌细胞系中敲低MALAT-1会降低细胞增殖，存活和迁移。我们先前在Panc 1细胞中观察到lncRNA HOTTIP和HOTAIR的类似结果;然而，MALAT-1调节的基因的RNAseq比较显示与HOTTIP/HOTAIR调节的基因的重叠最小。对MALAT-1敲低后基因表达变化的分析表明，这种lncRNA抑制了几种肿瘤抑制因子样基因，包括N-myc下调基因-1（NDRG-1），这是胰腺癌中的一种肿瘤抑制因子，也被EZH 2（PRC 2复合体成员）共同抑制。我们还观察到特异性蛋白Sp1、Sp3和Sp 4在Panc 1细胞中过表达，并且Sp敲低或用降低Sp蛋白表达的小分子处理也降低MALAT-1表达。我们还产生了分别为p53纯合子和杂合子的Kras过表达p53 L/L; LSL-KrasG 12 DL/+; p48 Cre +/-（p53 L/L/KrasG 12 D）和p53 L/+; LSLKrasG 12 DL/+; p48 Cre +/-（p53 L/+/KrasG 12 D）小鼠。这些小鼠迅速发展为胰腺导管腺癌样肿瘤，并与MALAT-1-/-小鼠杂交。我们观察到，在这些Ras过表达小鼠中，一个或两个MALAT-1等位基因的丢失并不显著影响死亡时间;然而，在p53-/+（杂合子）小鼠中，MALAT-1的丢失略微增加了它们的寿命。
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long non-coding RNA (lncRNA) that is a negative prognostic factor for patients with pancreatic cancer and several other tumors. In this study, we show that knockdown of MALAT-1 in Panc1 and other pancreatic cancer cell lines decreases cell proliferation, survival and migration. We previously observed similar results for the lncRNAs HOTTIP and HOTAIR in Panc1 cells; however, RNAseq comparison of genes regulated by MALAT-1 shows minimal overlap with HOTTIP/HOTAIR-regulated genes. Analysis of changes in gene expression after MALAT-1 knockdown shows that this lncRNA represses several tumor suppressor-like genes including N-myc downregulated gene-1 (NDRG-1), a tumor suppressor in pancreatic cancer that is also corepressed by EZH2 (a PRC2 complex member). We also observed that Specificity proteins Sp1, Sp3 and Sp4 are overexpressed in Panc1 cells and Sp knockdown or treatment with small molecules that decrease Sp proteins expression also decrease MALAT-1 expression. We also generated Kras-overexpressing p53L/L;LSL-KrasG12DL/+;p48Cre+/- (p53L/L/KrasG12D) and p53L/+;LSLKrasG12DL/+;p48Cre+/- (p53L/+/KrasG12D) mice which are p53 homo- and heterozygous, respectively. These mice rapidly develop pancreatic ductal adenocarcinoma-like tumors and were crossed with MALAT-1-/- mice. We observed that the loss of one or two MALAT-1 alleles in these Ras overexpressing mice does not significantly affect the time to death; however, the loss of MALAT-1 in the p53-/+ (heterozygote) mice slightly increases their lifespan.
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影响因子：
3.7
作者：
Ji Q;Liu X;Fu X;Zhang L;Sui H;Zhou L;Sun J;Cai J;Qin J;Ren J;Li Q
通讯作者：
Li Q
影响因子：
11.5
作者：
Fan, Yu;Shen, Bing;Liu, Yong
通讯作者：
Liu, Yong
长非编码 RNA MALAT-1 增强胰腺癌细胞中的干细胞样表型。
影响因子：
5.6
作者：
Jiao F;Hu H;Han T;Yuan C;Wang L;Jin Z;Guo Z;Wang L
通讯作者：
Wang L
影响因子：
8
作者：
Lin, R.;Maeda, S.;Edgington, T. S.
通讯作者：
Edgington, T. S.
影响因子：
3.3
作者：
Liby, Karen T.;Royce, Darlene B.;Sporn, Michael B.
通讯作者：
Sporn, Michael B.