title: Survival of motor neuron protein downregulates miR-9 expression in patients with spinal muscular atrophy.
abstract: 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.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Wang
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shyh-Shin
authors.initials: SS
authors.lastname: Chiou
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liao
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: jackhsu@kmu.edu.tw.
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein
keywords: Spinal muscular atrophy; Survival of motor neuron; miR-9
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