Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R.
Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R.
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DOI：
10.1371/journal.pone.0061015
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fontana JA
中科院分区：
文献类型：
--
作者：
Farhana L;Dawson MI;Murshed F;Das JK;Rishi AK;Fontana JA
MicroRNA参与了许多重要的细胞过程，包括细胞凋亡。我们以前发现，胰腺癌细胞凋亡诱导的金刚烷维甲酸相关（ARR）分子3-Cl-AHPC。在这里，我们报告了3-Cl-AHPC依赖性凋亡涉及调节许多microRNA，包括miR-150* 和miR-630。3-Cl-AHPC刺激胰腺癌细胞中miR-150* 的表达，并导致c-Myb和IGF-1 R的表达降低。3-Cl-AHPC介导的c-Myb减少导致c-Myb与IGF-1 R和Bcl-2启动子的结合减少，从而导致其转录和蛋白表达的抑制。miR-150* 的过表达也导致c-Myb和Bcl-2蛋白水平的降低。此外，添加miRNA抑制剂2 '-O-甲基化的miR-150可以阻止3-Cl-AHPC介导的miR-150* 水平的增加，并消除c-Myb蛋白的丢失。PANC-1细胞中c-Myb的敲低导致在存在或不存在3-Cl-AHPC的情况下增强的凋亡，证实了c-Myb的抗凋亡特性。miR-630的过表达还诱导胰腺癌细胞凋亡，并抑制靶蛋白IGF-1 R mRNA和蛋白的表达。总之，这些结果暗示了miR-150* 和miR-630及其靶向IGF-1 R促进胰腺癌细胞凋亡的关键作用。
MicroRNAs have been implicated in many critical cellular processes including apoptosis. We have previously found that apoptosis in pancreatic cancer cells was induced by adamantyl retinoid-related (ARR) molecule 3-Cl-AHPC. Here we report that 3-Cl-AHPC-dependent apoptosis involves regulating a number of microRNAs including miR-150* and miR-630. 3-Cl-AHPC stimulated miR-150* expression and caused decreased expression of c-Myb and IGF-1R in the pancreatic cancer cells. 3-Cl-AHPC-mediated reduction of c-Myb resulted in diminished binding of c-Myb with IGF-1R and Bcl-2 promoters, thereby causing repression of their transcription and protein expression. Over-expression of miR-150* also resulted in diminished levels of c-Myb and Bcl-2 proteins. Furthermore, the addition of the miRNA inhibitor 2′-O-methylated miR-150 blocked 3-Cl-AHPC-mediated increase in miR-150* levels and abrogated loss of c-Myb protein. Knockdown of c-Myb in PANC-1 cells resulted in enhanced apoptosis both in the presence or absence of 3-Cl-AHPC confirming the anti-apoptotic property of c-Myb. Overexpression of miR-630 also induced apoptosis in the pancreatic cancer cells and inhibited target protein IGF-1R mRNA and protein expression. Together these results implicate key roles for miR-150* and miR-630 and their targeting of IGF-1R to promote apoptosis in pancreatic cancer cells.
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影响因子：
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