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

12 Scopus citations

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

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Kamran, F., Andrade, A. C., Nella, A. A., Clokie, S. J., Rezvani, G., Nilsson, O., Baron, J., & 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