RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93.
RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93.
复制标题
RUNX1通过调节miR-93促进胰腺导管腺癌的侵袭性
DOI：
10.18632/oncotarget.20433
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发表时间：
2017-11-21
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Cheng Y;Yang H;Sun Y;Zhang H;Yu S;Lu Z;Chen J
runt相关转录因子1（RUNX1）是造血过程中的一个关键因子，介导造血干细胞和祖细胞（HSPCs）的规范和稳态，在几种实体人类癌症中也过表达，并与肿瘤进展相关。然而，RUNX1在胰腺导管腺癌中的表达和功能尚不清楚。在这里，我们发现RUNX1在胰腺腺癌组织中高度表达，并且降低RUNX1在胰腺细胞系中的侵袭性。此外，我们发现RUNX1可以负向调节miR-93的表达。生物信息学方法表明，miR-93前体启动子区存在两个结合位点，通过ChIP-qPCR和萤火虫荧光素酶报告基因检测，我们证实了这两个结合位点在同一种胰腺细胞系中均具有转录活性。这一结果支持了我们的假设，即RUNX1通过结合miR-93的启动子区来调节miR-93。此外，miR-93的表达和功能完全相反，miR-93过表达抑制胰腺癌细胞系的迁移和侵袭性，支持RUNX1负性调控miR-93。我们的研究结果为RUNX1作为癌基因通过抑制miR-93的作用提供了证据。靶向RUNX1可能是胰腺癌的潜在治疗策略。
Runt-related transcription factor 1(RUNX1), a key factor in hematopoiesis that mediates specification and homeostasis of hematopoietic stem and progenitor cells (HSPCs), is also overexpressed in several solid human cancers, and correlated with tumor progression. However, the expression and function of RUNX1 in pancreatic ductal adenocarcinoma were still unclear. Here, we show that RUNX1 is highly expressed in pancreatic adenocarcinoma tissues and knocking down of RUNX1 attenuated aggressiveness in pancreatic cell lines. Moreover, we found that RUNX1 could negatively regulate the expression of miR-93. Bioinformatics method showed that there are two binding sites in the the promotor region of miR-93 precursor and through ChIP-qPCR and firefly luciferase reporter assay, we vertified that these two binding sites each have transcriptive activity in one pancreatic cell lines. This result supported our presumption that RUNX1 regulate miR-93 through binding to the promotor region of miR-93. Besides, the expression and function of miR-93 is quite the opposite, miR-93 overexpression suppresses migration and invasiveness in pancreatic cell lines supporting that RUNX1 negatively regulated miR-93. Our findings provided evidence regarding the role of RUNX1 as an oncogene through the inhibition of miR-93. Targeting RUNX1 can be a potential therapeutic strategy in pancreatic cancer.
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影响因子：
64.8
作者：
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通讯作者：
Mardis, Elaine R.
影响因子：
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通讯作者：
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通讯作者：
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影响因子：
3.7
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