Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer

// Yonggang Tan 1, 2 , Hongzhuan Yin 3 , Heying Zhang 1 , Jun Fang 4 , Wei Zheng 1 , Dan Li 2 , Yue Li 2 , Wei Cao 2 , Cheng Sun 1 , Yusi Liang 1 , Juan Zeng 1 , Huawei Zou 1 , Weineng Fu 5 , Xianghong Yang 2 1 Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China 2 Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China 3 Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, P.R. China 4 Laboratory of Microbiology & Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan 5 Department of Medical Genetics, China Medical University, Shenyang, P.R. China Correspondence to: Xianghong Yang, e-mail: xianghongyoung@163.com Keywords: pancreatic cancer, miRNA, transcription factor, target gene Received: February 23, 2015      Accepted: May 13, 2015      Published: May 25, 2015 ABSTRACT 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.