TY - JOUR
T1 - Survival of motor neuron protein downregulates miR-9 expression in patients with spinal muscular atrophy
AU - Wang, Li Ting
AU - Chiou, Shyh Shin
AU - Liao, Yu Mei
AU - Jong, Yuh Jyh
AU - Hsu, Shih Hsien
N1 - Funding Information:
We are grateful to all families of patients with SMA for their kind cooperation as well as the support obtained by a grant from Kaohsiung Medical University ( KMUER007-4 ). This study was also supported by a grant from Kaohsiung Medical University Hospital ( KMUH-101-1M37 ). The authors would like to thank Enago ( www.enago.tw ) for the English language review.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Spinal muscular atrophy
KW - Survival of motor neuron
KW - miR-9
UR - http://www.scopus.com/inward/record.url?scp=84899427872&partnerID=8YFLogxK
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U2 - 10.1016/j.kjms.2013.12.007
DO - 10.1016/j.kjms.2013.12.007
M3 - Article
C2 - 24751385
AN - SCOPUS:84899427872
SN - 1607-551X
VL - 30
SP - 229
EP - 234
JO - Kaohsiung Journal of Medical Sciences
JF - Kaohsiung Journal of Medical Sciences
IS - 5
ER -
