title: Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer.
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.
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.|Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Heying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Microbiology & Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, P.R. China.
authors.forename: Weineng
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D020743:rhoB GTP-Binding Protein
keywords: miRNA; pancreatic cancer; target gene; transcription factor