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

Cody J Wehrkamp1, Sathish Kumar Natarajan1, Ashley M Mohr1

  • 1a Department of Biochemistry and Molecular Biology , Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center , Omaha.

RNA Biology
|December 30, 2017
PubMed

Insights

MicroRNA-106b (miR-106b) overexpression in cholangiocarcinoma represses anti-tumor genes. This study identified 112 repressed mRNAs, including KLF family members, revealing miR-106b’s role in cancer biology.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • MicroRNA (miRNA) dysregulation is common in cancer, altering gene expression.
  • miR-106b is an oncomiR overexpressed in cholangiocarcinoma, repressing anti-tumorigenic targets.

Purpose of the Study:

  • To identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells.
  • To perform a genome-wide, unbiased mRNA analysis to understand miR-106b's function.

Main Methods:

  • RNA sequencing (RNA-Seq) was employed for genome-wide mRNA analysis.
  • Validation of mRNA and protein targets was performed using established molecular biology techniques.

Main Results:

  • 112 mRNAs were found to be significantly repressed by miR-106b, with most containing the miR-106b seed-binding site.
  • 11 genes were validated at the mRNA level, and 7 proteins were shown to be regulated by miR-106b.
  • Novel targets Kruppel-like factor 2 (KLF2) and KLF6 were verified, along with regulation of four other KLF family members.

Conclusions:

  • miR-106b exhibits coordinated repression of multiple KLF family members.
  • This coordinated repression by miR-106b may contribute to cholangiocarcinoma tumor biology.
Keywords:
ApoptosisKLF10KLF11KLF13KLF2KLF4KLF6LKLFbiliary tract cancerlung Kruppel-like factormiR-106amiRNAnext-generation sequencing

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