Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

Donald E. Kuhn; Gerard J. Nuovo; Mickey M. Martin; Geraldine E. Malana; Adam P. Pleister; Jinmai Jiang; Thomas D. Schmittgen; Alvin V Terry; Katheleen Gardiner; Elizabeth Head; David S. Feldman; Terry S. Elton

doi:10.1016/j.bbrc.2008.03.120

Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

Donald E. Kuhn, Gerard J. Nuovo, Mickey M. Martin, Geraldine E. Malana, Adam P. Pleister, Jinmai Jiang, Thomas D. Schmittgen, Alvin V Terry, Katheleen Gardiner, Elizabeth Head, David S. Feldman, Terry S. Elton

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

139 Scopus citations

Abstract

Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.

Original language	English (US)
Pages (from-to)	473-477
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	370
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2008.03.120
State	Published - Jun 6 2008

Keywords

Brain
Cardiac
Down syndrome
In situ hybridization
MicroRNA
MicroRNA profiling
RT-PCR

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.03.120

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Kuhn, D. E., Nuovo, G. J., Martin, M. M., Malana, G. E., Pleister, A. P., Jiang, J., Schmittgen, T. D., Terry, A. V., Gardiner, K., Head, E., Feldman, D. S., & Elton, T. S. (2008). Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts. Biochemical and Biophysical Research Communications, 370(3), 473-477. https://doi.org/10.1016/j.bbrc.2008.03.120

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title = "Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts",

abstract = "Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.",

keywords = "Brain, Cardiac, Down syndrome, In situ hybridization, MicroRNA, MicroRNA profiling, RT-PCR",

author = "Kuhn, {Donald E.} and Nuovo, {Gerard J.} and Martin, {Mickey M.} and Malana, {Geraldine E.} and Pleister, {Adam P.} and Jinmai Jiang and Schmittgen, {Thomas D.} and Terry, {Alvin V} and Katheleen Gardiner and Elizabeth Head and Feldman, {David S.} and Elton, {Terry S.}",

note = "Funding Information: This work was supported by National Institutes of Health Grants #HL48848 (T.S.E.) and #HL084498 (D.S.F.), #ES012241 (A.V.T.), AG21912 (E.H.).",

year = "2008",

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doi = "10.1016/j.bbrc.2008.03.120",

language = "English (US)",

volume = "370",

pages = "473--477",

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AU - Kuhn, Donald E.

AU - Nuovo, Gerard J.

AU - Martin, Mickey M.

AU - Malana, Geraldine E.

AU - Pleister, Adam P.

AU - Jiang, Jinmai

AU - Schmittgen, Thomas D.

AU - Terry, Alvin V

AU - Gardiner, Katheleen

AU - Head, Elizabeth

AU - Feldman, David S.

AU - Elton, Terry S.

N1 - Funding Information: This work was supported by National Institutes of Health Grants #HL48848 (T.S.E.) and #HL084498 (D.S.F.), #ES012241 (A.V.T.), AG21912 (E.H.).

PY - 2008/6/6

Y1 - 2008/6/6

N2 - Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.

AB - Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.

KW - Brain

KW - Cardiac

KW - Down syndrome

KW - In situ hybridization

KW - MicroRNA

KW - MicroRNA profiling

KW - RT-PCR

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Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

Abstract

Keywords

ASJC Scopus subject areas

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