Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration

Fariha Kamran, Anenisia C. Andrade, Aikaterini A. Nella, Samuel J. Clokie, Geoffrey Rezvani, Ola Nilsson, Jeffrey Baron, Julian C. Lui

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Body growth is rapid in infancy but subsequently slows and eventually ceases due to a progressive decline in cell proliferation that occurs simultaneously in multiple organs. We previously showed that this decline in proliferation is driven in part by postnatal down-regulation of a large set of growth-promoting genes in multiple organs. We hypothesized that this growth-limiting genetic program is orchestrated by microRNAs (miRNAs). Bioinformatic analysis identified target sequences of the miR-29 family of miRNAs to be overrepresented in age-down-regulated genes. Concomitantly, expression microarray analysis in mouse kidney and lung showed that all members of the miR-29 family, miR-29a, -b, and -c, were strongly up-regulated from 1 to 6 weeks of age. Real-time PCR confirmed that miR-29a, -b, and -c were up-regulated with age in liver, kidney, lung, and heart, and their expression levels were higher in hepatocytes isolated from 5-week-old mice than in hepatocytes from embryonic mouse liver at embryonic day 16.5. We next focused on 3 predicted miR-29 target genes (Igf1, Imp1, and Mest), all of which are growth-promoting. A 3'-untranslated region containing the predicted target sequences from each gene was placed individually in a luciferase reporter construct. Transfection of miR-29 mimics suppressed luciferase gene activity for all 3 genes, and this suppression was diminished by mutating the target sequences, suggesting that these genes are indeed regulated by miR-29. Taken together, the findings suggest that up-regulation of miR-29 during juvenile life drives the down-regulation of multiple growth-promoting genes, thus contributing to physiological slowing and eventual cessation of body growth.

Original languageEnglish (US)
Pages (from-to)921-932
Number of pages12
JournalMolecular Endocrinology
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Deceleration
MicroRNAs
Up-Regulation
Growth
Genes
Luciferases
Hepatocytes
Down-Regulation
Kidney
Lung
Liver
3' Untranslated Regions
Microarray Analysis
Computational Biology
Transfection
Real-Time Polymerase Chain Reaction
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Kamran, F., Andrade, A. C., Nella, A. A., Clokie, S. J., Rezvani, G., Nilsson, O., ... Lui, J. C. (2015). Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration. Molecular Endocrinology, 29(6), 921-932. https://doi.org/10.1210/me.2015-1047

Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration. / Kamran, Fariha; Andrade, Anenisia C.; Nella, Aikaterini A.; Clokie, Samuel J.; Rezvani, Geoffrey; Nilsson, Ola; Baron, Jeffrey; Lui, Julian C.

In: Molecular Endocrinology, Vol. 29, No. 6, 01.06.2015, p. 921-932.

Research output: Contribution to journalArticle

Kamran, F, Andrade, AC, Nella, AA, Clokie, SJ, Rezvani, G, Nilsson, O, Baron, J & Lui, JC 2015, 'Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration', Molecular Endocrinology, vol. 29, no. 6, pp. 921-932. https://doi.org/10.1210/me.2015-1047
Kamran F, Andrade AC, Nella AA, Clokie SJ, Rezvani G, Nilsson O et al. Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration. Molecular Endocrinology. 2015 Jun 1;29(6):921-932. https://doi.org/10.1210/me.2015-1047
Kamran, Fariha ; Andrade, Anenisia C. ; Nella, Aikaterini A. ; Clokie, Samuel J. ; Rezvani, Geoffrey ; Nilsson, Ola ; Baron, Jeffrey ; Lui, Julian C. / Evidence that up-regulation of microRNA-29 contributes to postnatal body growth deceleration. In: Molecular Endocrinology. 2015 ; Vol. 29, No. 6. pp. 921-932.
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