Open AccessIdentification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke
Author(s) -
Xiaokui Guo,
Jialei Yang,
Baoyun Liang,
Tingting Shen,
Yan Yan,
Siyun Huang,
Jinying Zhou,
Jiao Huang,
Lian Gu,
Li Su
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000495058
Subject(s) - microrna , long non coding rna , fold change , microarray , messenger rna , biology , microarray analysis techniques , computational biology , gene expression , gene , bioinformatics , rna , genetics
Background/Aims: Long non-coding RNAs (lncRNAs) are potential biomarkers of tumors, cardiac disease, and cerebral disease because of their interaction with coding RNAs. This work focused on ischemic stroke (IS) and aimed to identify novel lncRNA biomarkers and construct lncRNA-related networks in IS. Methods: Differentially expressed lncRNAs were identified using Arraystar Human LncRNA Microarray v4.0, and validated with qRT-PCR. A lncRNA–mRNA co-expression network and a lncRNA–miRNA–mRNA regulatory network were constructed. Functional and pathway analyses were then performed. Results: In total, 560 up-regulated and 690 down-regulated differentially expressed lncRNAs were found (P < 0.05, false discovery rate < 0.05, absolute fold change ≥ 2). qRT-PCR results confirmed that lncRNA-ENST568297, lncRNA-ENST568243, and lncRNA-NR_046084 exhibited significant differential expression between IS and controls (all P < 0.05). Areas under the curves (AUCs) for these lncRNAs were 0.733, 0.743, and 0.690, respectively, and the combined AUC was 0.843. A coding–noncoding co-expression (CNC) network was constructed based on Pearson’s correlation coefficient. A specific lncRNA–miRNA–mRNA regulatory network of ENST568297, ENST568243, and NR_046084 was also constructed. Functional annotation of the up- and down-regulated mRNAs was performed. Pathway analysis enriched IS-related pathways with mRNAs in the lncRNA–miRNA–mRNA regulatory network. Conclusion: LncRNA and mRNA expression profiles in human peripheral blood were altered after IS. ENST568297, ENST568243, and NR_046084 were identified as novel potential diagnostic biomarkers of IS. Analysis of the CNC network and lncRNA–miRNA–mRNA regulatory network suggested that lncRNAs may participate in IS pathophysiology by regulating pivotal miRNAs, mRNAs, or IS-related pathways.