PDGF induced microRNA alterations in cancer cells.

PDGF induced microRNA alterations in cancer cells.
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DOI:
10.1093/nar/gkq1305
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发表时间:
2011-05
影响因子:
14.9
通讯作者:
Matei D
Matei D
中科院分区:
生物学2区
文献类型:
--
作者:
Shao M;Rossi S;Chelladurai B;Shimizu M;Ntukogu O;Ivan M;Calin GA;Matei D

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血小板衍生生长因子(PDGF)通过结合特异性受体调节基因转录。PDGF在脑肿瘤和其他肿瘤的发生中起关键作用,调节血管生成,并在生理条件下重塑基质。在这里,我们通过使用microRNA (miR)阵列显示PDGFs在胶质母细胞瘤和卵巢癌细胞中调节miRs的表达和功能。两种PDGF配体AA和BB以配体特异性的方式影响几种mir的表达;最强烈的变化包括PDGF-AA对let-7d的抑制和PDGF-BB对miR-146b的诱导。PDGF-BB诱导miR-146b是通过mapk依赖性诱导c-fos来调节的。我们证明PDGF通过miR改变来调节一些已知靶点(如cyclin D1)的表达,并确定表皮生长因子受体(EGFR)是PDGF- bb的新靶点。我们发现它的表达和功能被pdgf诱导的miR-146b抑制,并且miR-146b和EGFR在人胶质母细胞瘤中呈负相关。我们提出pdgf调控的基因转录涉及非编码rna的改变,并为癌细胞中mir依赖的反馈机制平衡生长因子受体信号提供证据。
Platelet derived growth factor (PDGF) regulates gene transcription by binding to specific receptors. PDGF plays a critical role in oncogenesis in brain and other tumors, regulates angiogenesis, and remodels the stroma in physiologic conditions. Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells. The two PDGF ligands AA and BB affect expression of several miRs in ligand-specific manner; the most robust changes consisting of let-7d repression by PDGF-AA and miR-146b induction by PDGF-BB. Induction of miR-146b by PDGF-BB is modulated via MAPK-dependent induction of c-fos. We demonstrate that PDGF regulates expression of some of its known targets (e.g. cyclin D1) through miR alterations and identify the epidermal growth factor receptor (EGFR) as a new PDGF-BB target. We show that its expression and function are repressed by PDGF-induced miR-146b and that mir-146b and EGFR correlate inversely in human glioblastomas. We propose that PDGF-regulated gene transcription involves alterations in non-coding RNAs and provide evidence for a miR-dependent feedback mechanism balancing growth factor receptor signaling in cancer cells.
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