Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells

•We obtained the expression profile of miRNAs in dengue virus infection in liver cells.•Let-7c is overexpressed in liver cells infected with DENV-2 and DENV-4.•Let-7c inhibits DENV infection.•BACH1 is down-regulated in liver cells infected with DENV probably through the inhibitory effect of let-7c.•...

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Published inVirus research Vol. 196; pp. 105 - 112
Main Authors Escalera-Cueto, Manuel, Medina-Martínez, Ingrid, del Angel, Rosa M., Berumen-Campos, Jaime, Gutiérrez-Escolano, Ana Lorena, Yocupicio-Monroy, Martha
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 22.01.2015
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Abstract •We obtained the expression profile of miRNAs in dengue virus infection in liver cells.•Let-7c is overexpressed in liver cells infected with DENV-2 and DENV-4.•Let-7c inhibits DENV infection.•BACH1 is down-regulated in liver cells infected with DENV probably through the inhibitory effect of let-7c.•HO-1 is overexpressed in DENV infection presumptively by BACH1 derepression. MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.
AbstractList •We obtained the expression profile of miRNAs in dengue virus infection in liver cells.•Let-7c is overexpressed in liver cells infected with DENV-2 and DENV-4.•Let-7c inhibits DENV infection.•BACH1 is down-regulated in liver cells infected with DENV probably through the inhibitory effect of let-7c.•HO-1 is overexpressed in DENV infection presumptively by BACH1 derepression. MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.
MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.
Author Medina-Martínez, Ingrid
del Angel, Rosa M.
Berumen-Campos, Jaime
Gutiérrez-Escolano, Ana Lorena
Yocupicio-Monroy, Martha
Escalera-Cueto, Manuel
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  surname: del Angel
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  givenname: Jaime
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  surname: Yocupicio-Monroy
  fullname: Yocupicio-Monroy, Martha
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  organization: Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Distrito Federal, Plantel del Valle, San Lorenzo 290, Col. Del Valle, México DF, CP 03100, Mexico
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Keywords Let-7c
miRNAs
Dengue virus
BACH1
Language English
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Snippet •We obtained the expression profile of miRNAs in dengue virus infection in liver cells.•Let-7c is overexpressed in liver cells infected with DENV-2 and...
MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been...
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SubjectTerms BACH1
Basic-Leucine Zipper Transcription Factors - genetics
Binding Sites
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - virology
Cell Line, Tumor
Dengue virus
Dengue Virus - genetics
Dengue Virus - metabolism
Fanconi Anemia Complementation Group Proteins - genetics
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Genome, Viral
Heme Oxygenase-1 - genetics
Host-Pathogen Interactions - genetics
Humans
Let-7c
MicroRNAs - genetics
miRNAs
Reproducibility of Results
RNA Interference
RNA, Viral
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Time Factors
Transfection
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virus Replication - genetics
Title Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells
URI https://dx.doi.org/10.1016/j.virusres.2014.11.010
https://www.ncbi.nlm.nih.gov/pubmed/25445350
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Volume 196
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