Open AccessSurvival of motor neuron protein downregulates miR‐9 expression in patients with spinal muscular atrophy
Author(s) -
Wang LiTing,
Chiou ShyhShin,
Liao YuMei,
Jong YuhJyh,
Hsu ShihHsien
Publication year - 2014
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2013.12.007
Subject(s) - spinal muscular atrophy , smn1 , sma* , motor neuron , medicine , microrna , transfection , downregulation and upregulation , small hairpin rna , microbiology and biotechnology , rna interference , cancer research , rna , biology , pathology , gene , disease , genetics , mathematics , combinatorics
Spinal muscular atrophy (SMA) is a lethal hereditary disease caused by homozygous absence of the survival of the motor neuron (SMN) 1 gene ( SMN1 ), and it is the leading genetic cause of infant mortality. The severity of SMA is directly correlated with SMN protein levels in affected patients; however, the cellular regulatory mechanisms for SMN protein expression are not completely understood. In this study, we investigated the regulatory effects between SMN expression and miR‐9a, a downstream noncoding small RNA. Using an inducible SMN short hairpin RNA interference (shRNAi) system in NSC 34 and human skin fibroblast cells, cellular miR‐9 levels and SMN protein repression were time‐dependently upregulated. Conversely, cellular miR‐9 levels decreased when HeLa cells were transfected with SMN protein fused with green fluorescent protein. In SMA‐like mice spinal cords and human primary skin fibroblasts isolated from patients with different degrees of SMA, human SMN exhibited a disease severity‐dependent decrease, whereas cellular miR‐9 levels increased. These results clearly suggested that cellular SMN proteins regulated miR‐9 expression and that miR‐9 expression was related to SMA severity. Thus, miR‐9 may be a marker for SMA prognosis.