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

1 Citation (Scopus)

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

Fingerprint

Kruppel-Like Transcription Factors
Cholangiocarcinoma
Messenger RNA
Genes
MicroRNAs
Seeds
Neoplasms
Proteins
Up-Regulation
Binding Sites
Genome
RNA
Gene Expression

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

Cite this

miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family. / Wehrkamp, Cody J.; Natarajan, Sathish K; Mohr, Ashley M.; Phillippi, Mary Anne; Mott, Justin L.

In: RNA Biology, Vol. 15, No. 3, 04.03.2018, p. 391-403.

Research output: Contribution to journalArticle

Wehrkamp, Cody J. ; Natarajan, Sathish K ; Mohr, Ashley M. ; Phillippi, Mary Anne ; Mott, Justin L. / miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family. In: RNA Biology. 2018 ; Vol. 15, No. 3. pp. 391-403.
@article{42c283a93a114947bf0def0f99c154da,
title = "miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family",
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.",
keywords = "Apoptosis, KLF10, KLF11, KLF13, KLF2, KLF4, KLF6, LKLF, biliary tract cancer, lung Kruppel-like factor, miR-106a, miRNA, next-generation sequencing",
author = "Wehrkamp, {Cody J.} and Natarajan, {Sathish K} and Mohr, {Ashley M.} and Phillippi, {Mary Anne} and Mott, {Justin L}",
year = "2018",
month = "3",
day = "4",
doi = "10.1080/15476286.2017.1422471",
language = "English (US)",
volume = "15",
pages = "391--403",
journal = "RNA Biology",
issn = "1547-6286",
publisher = "Landes Bioscience",
number = "3",

}

TY - JOUR

T1 - miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family

AU - Wehrkamp, Cody J.

AU - Natarajan, Sathish K

AU - Mohr, Ashley M.

AU - Phillippi, Mary Anne

AU - Mott, Justin L

PY - 2018/3/4

Y1 - 2018/3/4

N2 - 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.

AB - 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.

KW - Apoptosis

KW - KLF10

KW - KLF11

KW - KLF13

KW - KLF2

KW - KLF4

KW - KLF6

KW - LKLF

KW - biliary tract cancer

KW - lung Kruppel-like factor

KW - miR-106a

KW - miRNA

KW - next-generation sequencing

UR - http://www.scopus.com/inward/record.url?scp=85041310055&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041310055&partnerID=8YFLogxK

U2 - 10.1080/15476286.2017.1422471

DO - 10.1080/15476286.2017.1422471

M3 - Article

C2 - 29286255

AN - SCOPUS:85041310055

VL - 15

SP - 391

EP - 403

JO - RNA Biology

JF - RNA Biology

SN - 1547-6286

IS - 3

ER -