PMID- 21559394
OWN - NLM
STAT- MEDLINE
DCOM- 20111128
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 4
DP  - 2011 Apr 29
TI  - Microbiota modulate host gene expression via microRNAs.
PG  - e19293
LID - 10.1371/journal.pone.0019293 [doi]
LID - e19293
AB  - Microbiota are known to modulate host gene expression, yet the underlying 
      molecular mechanisms remain elusive. MicroRNAs (miRNAs) are importantly 
      implicated in many cellular functions by post-transcriptionally regulating gene 
      expression via binding to the 3'-untranslated regions (3'-UTRs) of the target 
      mRNAs. However, a role for miRNAs in microbiota-host interactions remains 
      unknown. Here we investigated if miRNAs are involved in microbiota-mediated 
      regulation of host gene expression. Germ-free mice were colonized with the 
      microbiota from pathogen-free mice. Comparative profiling of miRNA expression 
      using miRNA arrays revealed one and eight miRNAs that were differently expressed 
      in the ileum and the colon, respectively, of colonized mice relative to germ-free 
      mice. A computational approach was then employed to predict genes that were 
      potentially targeted by the dysregulated miRNAs during colonization. Overlapping 
      the miRNA potential targets with the microbiota-induced dysregulated genes 
      detected by a DNA microarray performed in parallel revealed several host genes 
      that were regulated by miRNAs in response to colonization. Among them, Abcc3 was 
      identified as a highly potential miRNA target during colonization. Using the 
      murine macrophage RAW 264.7 cell line, we demonstrated that mmu-miR-665, which 
      was dysregulated during colonization, down-regulated Abcc3 expression by directly 
      targeting the Abcc3 3'-UTR. In conclusion, our study demonstrates that microbiota 
      modulate host microRNA expression, which could in turn regulate host gene 
      expression.
FAU - Dalmasso, Guillaume
AU  - Dalmasso G
AD  - Division of Digestive Diseases, Department of Medicine, Emory University School 
      of Medicine, Atlanta, Georgia, United States of America. gdalmas@emory.edu
FAU - Nguyen, Hang Thi Thu
AU  - Nguyen HT
FAU - Yan, Yutao
AU  - Yan Y
FAU - Laroui, Hamed
AU  - Laroui H
FAU - Charania, Moiz A
AU  - Charania MA
FAU - Ayyadurai, Saravanan
AU  - Ayyadurai S
FAU - Sitaraman, Shanthi V
AU  - Sitaraman SV
FAU - Merlin, Didier
AU  - Merlin D
LA  - eng
GR  - R24-DK-064399/DK/NIDDK NIH HHS/United States
GR  - R01 DK055850/DK/NIDDK NIH HHS/United States
GR  - R01 DK071594/DK/NIDDK NIH HHS/United States
GR  - R24 DK064399/DK/NIDDK NIH HHS/United States
GR  - R01-DK-071594/DK/NIDDK NIH HHS/United States
GR  - R01-DK-55850/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110429
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3' Untranslated Regions)
RN  - 0 (DNA, Complementary)
RN  - 0 (MicroRNAs)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 1YV0492L5Z (multidrug resistance-associated protein 3)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Cell Line
MH  - Computational Biology/methods
MH  - DNA, Complementary/metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Green Fluorescent Proteins/metabolism
MH  - Metagenome/*genetics
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Multidrug Resistance-Associated Proteins/metabolism
MH  - Oligonucleotide Array Sequence Analysis
PMC - PMC3084815
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/05/12 06:00
MHDA- 2011/12/13 00:00
PMCR- 2011/04/29
CRDT- 2011/05/12 06:00
PHST- 2010/12/16 00:00 [received]
PHST- 2011/03/28 00:00 [accepted]
PHST- 2011/05/12 06:00 [entrez]
PHST- 2011/05/12 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2011/04/29 00:00 [pmc-release]
AID - PONE-D-10-06671 [pii]
AID - 10.1371/journal.pone.0019293 [doi]
PST - epublish
SO  - PLoS One. 2011 Apr 29;6(4):e19293. doi: 10.1371/journal.pone.0019293.