The Expression Discrepancy and Characteristics of Long Non-Coding RNAs in Peripheral Blood Leukocytes From Amyotrophic Lateral Sclerosis Patients

Abstract

Background Amyotrophic lateral sclerosis (ALS) is known to be a progressive neurodegenerative disease that affects upper and lower motor neurons. Less than 10% of ALS patients are defined as familial ALS, more than 90% are sporadic ALS (SALS). According to the genomic information described in existing databases, up to 98% of the human genome consists of non-coding sequences. And of these, nearly 40% of long non-coding RNAs (lncRNAs) are specifically expressed in the brain. Hence, we believe the discrepancy of lncRNAs expression plays a key role in neurodegenerative diseases. It is demanded to search for potential lncRNA biomarkers of SALS and find their involvement in related disease mechanisms. Methods We screened 30 lncRNAs with altered expression from peripheral blood leukocytes of SALS patients by microarray and validated 13 of them in leukocytes of SALS, Parkinson's disease (PD) patients and healthy controls (HC). The statistical evaluation of expression was performed by the two-tailed Mann-Whitney U test for means between groups. We followed the bioinformatics to perform a functional enrichment analysis of co-expressed mRNAs, transcription factors and lncRNAs for functional prediction. Co-expressed mRNAs of lncRNAs were identified by calculating Pearson Correlation. Results We identified lnc-DYRYK2-7:1, lnc-ABCA12-3:1 and lnc-POTEM-4:7 show decreased expression in SALS patients, whereas in PD patients they show increased expression or no change. In addition, expression of lnc-CNTN4-2:1 and lnc-NR3C2-8:1 were decreased in both SALS and PD patients. We found that XIST was only reduced in male patients with SALS and PD, and not in female patients with SALS but was elevated in PD by gender grouping. Furthermore, we performed GO term enrichment and KEGG pathway analysis for lncRNAs showing differential expression in microarray. We discovered that a significant proportion of differential expressed lncRNAs were associated with various signaling pathways and transcription factors which are consistent with other clinical findings. Conclusion Our study enriches the analysis of lncRNA transcriptome sequencing for ALS and PD to date. We validated 3 lncRNA transcripts with specific expression differences only in SALS patients and investigated the bioinformatics information of lncRNAs for subsequent functional studies related to neurodegenerative diseases.