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The Regulatory Network Menin-MicroRNA 26a As a Possible Target for RNA-Based Therapy of Bone Diseases

joseay963 添加于 2012-4-9 15:28 | 1775 次阅读 | 0 个评论

作者
Luzi E, Marini F, Tognarini I, Galli G, Falchetti A, Brandi ML
摘要
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, interplaying with transcription factors in complex regulatory networks. Menin is the product of the MEN1 oncosuppressor gene, responsible for multiple endocrine neoplasia type 1 syndrome. Recent data suggest that menin functions as a general regulator of transcription. Menin expression modulates mesenchymal cell commitment to the myogenic or osteogenic lineages. The microRNA 26a (miR-26a) modulates the expression of SMAD1 protein during the osteoblastic differentiation of human adipose tissue-derived stem cells (hADSCs). We used siRNA silencing against MEN1 mRNA and pre-miR-26 mimics to study the interplay between them and to investigate the interplay between menin and miR-26a as regulators of osteogenic differentiation in the hADSCs. We found that in hADSCs the siRNA-induced silencing of MEN1 mRNA resulted in a down regulation of miR-26a, with a consequent up-regulation of SMAD1 protein. Chromatin immunoprecipitation (ChIP) showed that menin occupies the miR-26-a gene promoter, thus inducing its expression and confirming that menin is a positive regulator of miR-26a. In conclusion, results from this study evidenced, for the first time, a direct interaction between menin transcription factor and miRNA, interaction that seems to play a pivotal role during the hADSCs osteogenesis, thus suggesting a novel target for bone disease RNA-based therapy.
详细资料
- 文献种类:期刊
- 期刊名称: Nucleic Acid Therapeutics
- 期刊缩写: Nucleic Acid Ther
- 期卷页: 2012年第22卷第2期 103-108页
- 地址: Metabolic Bone Unit, Department of Internal Medicine, University of Florence , Florence, Italy
- ISBN: 2159-3345
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