Differential expression profile study and gene function analysis of maternal foetal-derived circRNA for screening for Down's syndrome

Weiguo Sui; Qing Gan; Yan Chang; Minglin Ou; Jiejing Chen; Hua Lin; Wen Xue; Yan Wu; Huiyan He; Donge Tang; Yong Dai

doi:10.3892/etm.2019.8288

Differential expression profile study and gene function analysis of maternal foetal-derived circRNA for screening for Down's syndrome

Exp Ther Med. 2020 Feb;19(2):1006-1016. doi: 10.3892/etm.2019.8288. Epub 2019 Dec 5.

Authors

Weiguo Sui^{1

2}, Qing Gan^{1

2}, Yan Chang³, Minglin Ou^{1

2}, Jiejing Chen^{1

2}, Hua Lin^{1

2}, Wen Xue^{1

2}, Yan Wu⁴, Huiyan He⁴, Donge Tang⁴, Yong Dai^{1

2

4}

Affiliations

¹ Guangxi Key Laboratory of Metabolic Diseases Research, Guilin No. 924 Hospital, Guilin, Guangxi 541002, P.R. China.
² Kidney Diseases Research, Department of Nephrology, Guilin No. 924 Hospital, Guilin, Guangxi 541002, P.R. China.
³ Reproductive Center, Guilin No. 924 Hospital, Guilin, Guangxi 541002, P.R. China.
⁴ Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.

Abstract

Recent studies have shown that circular RNAs (circRNAs) exhibit differential expression in certain diseases. However, to the best of our knowledge, maternal fetal-derived circRNAs and mRNAs associated with Down's syndrome (DS) have not yet been investigated. A total of 12 umbilical cord blood samples were collected from pregnant women, including six women carrying fetuses with DS (diagnosed by G-banding karyotype analysis), and six women carrying fetuses without DS. In addition, 12 peripheral blood samples were obtained from children, including six children with DS and six children without DS. Gene chip technology was used to screen for differentially expressed circRNAs and mRNAs in the cord blood samples, and were subsequently verified by reverse transcription-quantitative polymerase chain reaction in peripheral blood from the children to identify potential biomarkers. Furthermore, circRNA/microRNA (miRNA) interactions were predicted using Arraystar miRNA target prediction software. There was a significant difference in the expression of hsa_circRNA_103127, hsa_circRNA_103112 and hsa_circRNA_104907 between cord blood obtained from the women carrying fetuses with and without DS, and between peripheral blood obtained from children with and without DS (P<0.01). As hsa_circRNA_103112 exhibited significant differences in expression between cord blood obtained from the women carrying fetuses with and without DS and between peripheral blood obtained from children with and without DS, its corresponding gene, ubiquitin specific peptidase 25, may be involved in the pathogenesis of the condition. These results suggested that hsa_circRNA_103112 may be upregulated in individuals with DS, resulting in an expression imbalance of diploid genes through interactions among circRNA, miRNA and mRNA. Therefore, the level of hsa_circRNA_103112 in the peripheral blood of a pregnant woman may serve as potential biomarker of fetal DS during non-invasive prenatal screening.

Keywords: Down's syndrome; circular RNA; differential expression; fetal; gene function; maternal.