miR-106b aberrantly expressed in a double transgenic mouse model for Alzheimer's disease targets TGF-β type II receptor.

Abstract

MicroRNAs (miRNAs) are abundantly expressed in the brain and play an important role in disorders of the brain, including Alzheimer's diseases (AD). Growing body of evidence suggests that the TGF-β signaling pathway plays a key role in the pathogenesis of AD. However, it is unclear whether miRNAs involved in AD pathogenesis by regulating TGF-β signaling. Here we found that miR-106b and TGF-β type II receptor (TβR II) were aberrantly expressed in APPswe/PS∆E9 mice (a double transgenic mouse model for AD). Sequence analysis revealed two putative binding sites for miR-106b in the 3' UTR of the TβR II mRNA. Our results showed that the expression of miR-106b was inversely correlated with TβR II protein levels and miR-106b can directly inhibit the TβR II translation in vitro. After induced neurodifferentiation with all-trans retinoic acid, we observed significant neurodegeneration in SH-SY5Y cells stably transfected with miR-106b. Western blot analysis revealed unchanged total Smad2/3 protein levels, but reduced phospho-Smad2/3 (p-Smad2/3) and increased Smad6/7 protein levels in the miR-106b stably transfected cell line. Exposure of SH-SY5Y cells to Aβ42 oligomers led to the expression of miR-106b was first increased and then decreased and TβR II levels reduced. Our in vitro results suggested that Aβ42 oligomer-induced miR-106b leads to impairment in TGF-β signaling through TβR II, concomitant with retinoic acid-induced neurodegeneration in SH-SY5Y cells. These results show that TβR II is a functional target of miR-106b and that miR-106b may influence TGF-β signaling, thereby contributing to the pathogenesis of AD.

• Authors: Hailin Wang, Jialin Liu, Yuanyuan Zong, Yanfeng Xu, Wei Deng, Hua Zhu, Ying Liu, Chunmei Ma, Lan Huang, Lianfeng Zhang, Chuan Qin
• Journal: Brain research (Brain Res) Vol. 1357 Pg. 166-74 (Oct 21 2010) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 20709030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• MicroRNAs
• Mirn106 microRNA, mouse
• Receptors, Transforming Growth Factor beta
• Smad Proteins
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Alzheimer Disease (genetics, metabolism)
• Animals
• Blotting, Western
• Brain (metabolism)
• Cell Line
• Cell Survival (physiology)
• Cells, Cultured
• Disease Models, Animal
• Mice
• Mice, Transgenic
• MicroRNAs (genetics)
• Neurons (metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Smad Proteins (genetics, metabolism)