Survival of motor neuron protein downregulates miR-9 expression in patients with spinal muscular atrophy

Li Ting Wang, Shyh Shin Chiou, Yu Mei Liao, Yuh Jyh Jong, Shih Hsien Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)229-234
Number of pages6
JournalKaohsiung Journal of Medical Sciences
Volume30
Issue number5
DOIs
Publication statusPublished - 2014 May
Externally publishedYes

Keywords

  • miR-9
  • Spinal muscular atrophy
  • Survival of motor neuron

ASJC Scopus subject areas

  • Medicine(all)

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