Abstract
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.
Highlights
Pancreatic ductal adenocarcinoma remains to be one of the most lethal malignancies worldwide, which ranks the fourth, fourth and sixth leading cause of cancer-related deaths in the United States, European Union and China, respectively [1,2,3]
To evaluate whether RUNX1 protein expression is increased in pancreatic cancer, immunohistochemistry for RUNX1 was done in 39 pancreatic ductal adenocarcinoma (PDAC) cases, each including tumor and normal tissues in the same slide
We confirmed that the transcription factor, RUNX1, is upregulated in PDAC and plays many roles supporting tumor progression
Summary
Pancreatic ductal adenocarcinoma remains to be one of the most lethal malignancies worldwide, which ranks the fourth, fourth and sixth leading cause of cancer-related deaths in the United States, European Union and China, respectively [1,2,3]. Because of their retroperitoneal location and no reliable early diagnostic markers, over 80% patients have been in the advancedstage at diagnosis [4]. The RUNX (Runt-related transcription factor) family of genes are significant regulators controlling pancreatic cancer progression. Mutations of transcription factor CBFB and deletions of RUNX1 causing Runx1/
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