miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family

Cody J. Wehrkamp, Sathish K Natarajan, Ashley M. Mohr, Mary Anne Phillippi, Justin L Mott

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

MicroRNA dysregulation is a common feature of cancer and due to the promiscuity of microRNA binding this can result in a wide array of genes whose expression is altered. miR-106b is an oncomiR overexpressed in cholangiocarcinoma and its upregulation in this and other cancers often leads to repression of anti-tumorigenic targets. The goal of this study was to identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells using a genome-wide, unbiased mRNA analysis. Through RNA-Seq we found 112 mRNAs significantly repressed by miR-106b. The majority of these genes contain the specific miR-106b seed-binding site. We have validated 11 genes from this set at the mRNA level and demonstrated regulation by miR-106b of 7 proteins. Combined analysis of our miR-106b-regulated mRNA data set plus published reports indicate that miR-106b binding is anchored by G:C pairing in and near the seed. Novel targets Kruppel-like factor 2 (KLF2) and KLF6 were verified both at the mRNA and at the protein level. Further investigation showed regulation of four other KLF family members by miR-106b. We have discovered coordinated repression of multiple members of the KLF family by miR-106b that may play a role in cholangiocarcinoma tumor biology.

Original languageEnglish (US)
Pages (from-to)391-403
Number of pages13
JournalRNA Biology
Volume15
Issue number3
DOIs
StatePublished - Mar 4 2018

Keywords

  • Apoptosis
  • KLF10
  • KLF11
  • KLF13
  • KLF2
  • KLF4
  • KLF6
  • LKLF
  • biliary tract cancer
  • lung Kruppel-like factor
  • miR-106a
  • miRNA
  • next-generation sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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