| First Author | Wang H | Year | 2010 |
| Journal | Brain Res | Volume | 1357 |
| Pages | 166-74 | PubMed ID | 20709030 |
| Mgi Jnum | J:165149 | Mgi Id | MGI:4836328 |
| Doi | 10.1016/j.brainres.2010.08.023 | Citation | Wang H, et al. (2010) miR-106b aberrantly expressed in a double transgenic mouse model for Alzheimer's disease targets TGF-beta type II receptor. Brain Res 1357:166-74 |
| abstractText | 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-beta signaling pathway plays a key role in the pathogenesis of AD. However, it is unclear whether miRNAs involved in AD pathogenesis by regulating TGF-beta signaling. Here we found that miR-106b and TGF-beta type II receptor (TbetaR II) were aberrantly expressed in APPswe/PSE9 mice (a double transgenic mouse model for AD). Sequence analysis revealed two putative binding sites for miR-106b in the 3' UTR of the TbetaR II mRNA. Our results showed that the expression of miR-106b was inversely correlated with TbetaR II protein levels and miR-106b can directly inhibit the TbetaR 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 Abeta42 oligomers led to the expression of miR-106b was first increased and then decreased and TbetaR II levels reduced. Our in vitro results suggested that Abeta42 oligomer-induced miR-106b leads to impairment in TGF-beta signaling through TbetaR II, concomitant with retinoic acid-induced neurodegeneration in SH-SY5Y cells. These results show that TbetaR II is a functional target of miR-106b and that miR-106b may influence TGF-beta signaling, thereby contributing to the pathogenesis of AD. |
