hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration, invasion, and side populations.

hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration, invasion, and side populations.
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hsa-miR-520h 下调胰腺癌细胞中的 ABCG2 以抑制迁移、侵袭和旁群

DOI:
10.1038/sj.bjc.6605724
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发表时间:
2010-08-10
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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背景:ABCG 2在胰腺中通常不表达或表达较低,但在人胰腺癌细胞中表达较高。ABCG 2在人类cancers.Methods中被改变的机制仍然未知:我们研究了ABCG 2在四种胰腺癌细胞系中的表达,并使用了三种microRNA(miRNA)靶向预测程序,以及现有文献中的信息来预测和鉴定hsa-miR-520 h作为靶向ABCG 2的miRNA。结果:转染胰腺癌细胞PANC-1后,ABCG 2的mRNA和蛋白水平均降低,提示ABCG 2是hsa-miR-520 h的靶基因。将hsa-miR-520 h模拟物引入PANC-1细胞中也导致细胞迁移和侵袭的抑制以及侧群细胞的减少。细胞增殖,细胞周期进程和凋亡没有受到影响。结论:我们提出,hsa-miR-520 h的影响可能是,至少部分,由其ABCG 2的调节。因此,我们的研究结果提供了一个新的见解,在胰腺癌中的ABCG 2表达的调节miRNA的功能。因此,使用miRNA模拟物的基因疗法可用作胰腺癌疗法。
Background:Expression of ABCG2 is normally absent or low in the pancreas, but high in human pancreatic cancer cells. The mechanism by which ABCG2 is altered in human cancers remains unknown.Methods:We investigated ABCG2 expression in four pancreatic cancer cell lines, and used three microRNA (miRNA) target prediction programmes, and information from the existing literature to predict and identify hsa-miR-520h as an miRNA that targets ABCG2. The function of this miRNA was investigated by transient transfection of the pancreatic cancer cell line PANC-1 with oligonucleotides that mimic hsa-miR-520h.Results:Results showed that both mRNA and protein levels of ABCG2 were reduced, indicating that it was a target of hsa-miR-520h. Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted in inhibition of cell migration and invasion, and reduction of side population cells. Cell proliferation, cell cycle progression and apoptosis were not affected.Conclusions:We propose that the effects of hsa-miR-520h may be, at least in part, caused by its regulation of ABCG2. Thus, our findings provide a new insight into the function of miRNA in the regulation of ABCG2 expression in pancreatic cancer. Gene therapy using miRNA mimics may therefore be useful as a pancreatic cancer therapy.
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