Cargando…

RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Yin, Yang, Haiyan, Sun, Yang, Zhang, Hongkai, Yu, Shuangni, Lu, Zhaohui, Chen, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725115/
https://www.ncbi.nlm.nih.gov/pubmed/29245924
http://dx.doi.org/10.18632/oncotarget.20433
_version_ 1783285481078784000
author Cheng, Yin
Yang, Haiyan
Sun, Yang
Zhang, Hongkai
Yu, Shuangni
Lu, Zhaohui
Chen, Jie
author_facet Cheng, Yin
Yang, Haiyan
Sun, Yang
Zhang, Hongkai
Yu, Shuangni
Lu, Zhaohui
Chen, Jie
author_sort Cheng, Yin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5725115
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-57251152017-12-14 RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93 Cheng, Yin Yang, Haiyan Sun, Yang Zhang, Hongkai Yu, Shuangni Lu, Zhaohui Chen, Jie Oncotarget Research Paper 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. Impact Journals LLC 2017-08-24 /pmc/articles/PMC5725115/ /pubmed/29245924 http://dx.doi.org/10.18632/oncotarget.20433 Text en Copyright: © 2017 Cheng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cheng, Yin
Yang, Haiyan
Sun, Yang
Zhang, Hongkai
Yu, Shuangni
Lu, Zhaohui
Chen, Jie
RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title_full RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title_fullStr RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title_full_unstemmed RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title_short RUNX1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating miR-93
title_sort runx1 promote invasiveness in pancreatic ductal adenocarcinoma through regulating mir-93
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725115/
https://www.ncbi.nlm.nih.gov/pubmed/29245924
http://dx.doi.org/10.18632/oncotarget.20433
work_keys_str_mv AT chengyin runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT yanghaiyan runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT sunyang runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT zhanghongkai runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT yushuangni runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT luzhaohui runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93
AT chenjie runx1promoteinvasivenessinpancreaticductaladenocarcinomathroughregulatingmir93