Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer
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Yonggang Tan1,2, Hongzhuan Yin3, Heying Zhang1, Jun Fang4, Wei Zheng1, Dan Li2, Yue Li2, Wei Cao2, Cheng Sun1, Yusi Liang1, Juan Zeng1, Huawei Zou1, Weineng Fu5, Xianghong Yang2
1Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China
2Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China
3Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, P.R. China
4Laboratory of Microbiology & Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
5Department of Medical Genetics, China Medical University, Shenyang, P.R. China
Xianghong Yang, e-mail: [email protected]
Keywords: pancreatic cancer, miRNA, transcription factor, target gene
Received: February 23, 2015 Accepted: May 13, 2015 Published: May 25, 2015
Cancer treatment alters microRNA (miRNA) expression, revealing potential therapeutic targets (oncotarget). Here we treated pancreatic cancer (ASPC-1) cells with either recombinant human endostatin (rh-endostatin) or gemcitabine. Then high-throughput sequencing assay was performed to screen for altered miRNAs. Both treatments decreased levels of MiR-19a. We found that miR-19a stimulated cell proliferation, migration, invasion in vitro and tumor growth in vivo. High levels of miR-19a correlated with poor prognosis in patients. Ras homolog family member B (RHOB) was identified as a direct target of miR-19a. Furthermore, RHOB was down-regulated in human pancreatic cancer samples. Restoration of RHOB induced apoptosis, inhibited proliferation and migration of ASPC-1 cells. SP-1 was identified as an upstream transcription factor of miR-19a gene, promoting miR-19a transcription. Rh-endostatin decreased miR-19a expression by down-regulating SP-1. These findings suggest that miR-19a is a potential therapeutic target in pancreatic cancer.
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