Article

Correlation of the predisposition of Chinese children to cerebral palsy with nucleotide variation in primiR- 124 that alters the non-canonical apoptosis pathway

Authors: Hui LI1, Xiu-li WANG2, Yan-qiu WU1, Xiu-mei LIU1, Ai-min LI1
1 Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China
2 Department of Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China
Correspondence to: Ai-min LI: woxinfeiyang_7777@126.com,
DOI: 10.1038/aps.2017.211
Received: 22 August 2017
Accepted: 14 December 2017
Advance online: 17 May 2018

Abstract

Cerebral palsy (CP) is a group of non-progressive motor impairment syndromes caused by brain lesions during development. Herein, we investigated the relationship between nucleotide variations in a miRNA coding region and the predisposition of Chinese children to cerebral palsy. A total of 233 CP patients and 256 healthy participants were enrolled, and 60 children were selected from each group for plasma miRNA detection. We screened the coding regions of pri-miR-124-1, -2, and -3 using PCR and sequencing. The expression of miR-124 was determined by qRT-PCR. Luciferase assays and Western blots were used to confirm the regulation of target genes by miR-124. The function of miR-124 was further identified in SH-SY5Y cells by detecting cell viability and apoptosis. We revealed that the rare alleles T of rs3802169 and G of rs191727850 were found to be associated with an increased risk of cerebral palsy (OR=3.71, 95% CI 1.74–7.92 and OR=2.18, 95% CI 1.36–3.49, respectively). We further showed that the levels of mature miR-124 were down-regulated by the C-to-T variation in vitro. More importantly, the reduction of miR-124 resulting from the C-to-T change led to the less-efficient inhibition of the target genes ITGB1, LAMC1 and BECN1, which may play important roles during the development of the nervous system. Meanwhile, the reduction in the expression of miR-124 was also related to the increased nuclear translocation of apoptosis-inducing factor (AIF) under oxidative stress, thereby inducing more cell apoptosis. Our results suggest that one functional polymorphism in pri-miR-124-1 might contribute to the genetic predisposition of Chinese children to cerebral palsy by disrupting the production of miR-124, which consequently interfered in the expression and function of the target genes of miR-124.
Keywords: cerebral palsy; miR-124; polymorphism; non-canonical apoptosis pathway; Chinese children

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