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

Oncotarget. 2015 Jul 10;6(19):17391-403. doi: 10.18632/oncotarget.3975.

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.

Keywords: miRNA; pancreatic cancer; target gene; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / biosynthesis*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Real-Time Polymerase Chain Reaction
  • Sp1 Transcription Factor / metabolism*
  • Transfection
  • Up-Regulation
  • rhoB GTP-Binding Protein / biosynthesis*

Substances

  • MIRN19 microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • SP1 protein, human
  • rhoB GTP-Binding Protein