miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor.
miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor.
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DOI：
10.1016/j.bbrc.2011.02.065
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发表时间：
2011-03-25
影响因子：
3.1
通讯作者：
Schmittgen, Thomas D.
中科院分区：
文献类型：
--
作者：
Park, Jong-Kook;Henry, Jon C.;Jiang, Jinmai;Esau, Christine;Gusev, Yuriy;Lerner, Megan R.;Postier, Russell G.;Brackett, Daniel J.;Schmittgen, Thomas D.
据报道，许多microrna （miRNA）在癌症中存在差异表达，然而，许多miRNA在癌症中失调的后果尚不清楚。我们报道了位于17p13染色体上的两个mirna miR-132和miR-212在胰腺腺癌（PDAC）组织中过表达。预计这两种mirna都靶向视网膜母细胞瘤肿瘤抑制因子Rb1。在转染了pre-miR-212和pre-miR-132寡核苷酸的胰腺癌细胞系中，荧光素酶报告基因试验和western blot证实了这种相互作用的有效性。转染pre-miR-132/-212寡核苷酸的Panc-1细胞增殖增强。相反，miR-132/-212的反义寡核苷酸减少细胞增殖并导致G2/M细胞周期阻滞。在过表达miR-132/-212的细胞中，许多E2F转录靶点的mRNA增加。将Panc-1细胞暴露于β2肾上腺素能受体激动剂特布他林后，miR-132和miR-212的表达增加了2至4倍。我们报道，miR-132和miR-212的过表达导致胰腺癌细胞中pRb蛋白的减少，并且这些mirna的过表达可能是由于几种E2F靶基因的表达增加而导致细胞增殖的增加。β2肾上腺素能通路可能在这一新机制中发挥重要作用。
Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G2/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2 to 4 fold. We report that over expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism.
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影响因子：
4.1
作者：
Remenyi, Judit;Hunter, Christopher J.;Arthur, J. Simon C.
通讯作者：
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影响因子：
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影响因子：
6.4
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通讯作者：
Schmittgen, Thomas D.
影响因子：
6.4
作者：
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通讯作者：
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