Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke

Cell Mol Neurobiol. 2022 Jan;42(1):265-278. doi: 10.1007/s10571-020-00918-y. Epub 2020 Jul 11.

Abstract

Long non-coding RNAs (lncRNAs) can not only regulate gene transcription and translation, but also participate in the development of central nervous system diseases as epigenetic modification factors. However, their functional significance in atherosclerosis-induced ischemic stroke (AIIS) is unclear. The study aimed to screen out differentially expressed lncRNAs (delncRNAs), and to elucidate their potential regulatory mechanisms in the pathophysiology of AIIS. Based on the clinicopathological features and clinical images, we screened out 10 patients with AIIS and recruited 10 healthy volunteers. Then we used microarray to detect the whole blood RNA of subjects, and explored the biological functions of delncRNAs by GO and KEGG analysis. After further analyzing the delncRNAs of THP-1 stimulated with ox-LDL, selective lncRNAs were screened and a corresponding lncRNA-mRNA interaction network was constructed through co-expression analysis. We yielded 180 delncRNAs (44 up-regulated and 136 down-regulated) and 218 demRNAs (45 up-regulated and 173 down-regulated). Lnc-SCARNA8 and lnc-SNRPN-2 are the most significant elevated and decreased lncRNA in AIIS, respectively. The delncRNAs may play a significant role in ubiquitination-mediated protein degradation signaling pathways. According to lncRNA-mRNA network, the expression of vacuolar protein sorting 13 homolog B (VPS13B) and biliverdin reductase B (BLVRB) were significantly regulated. Our findings suggest that the ubiquitinated proteasome pathway, VPS13B and BLVRB may play a fundamental role in the pathological process of AIIS.

Keywords: Atherosclerosis; Ischemic stroke; LncRNA; Transcriptome.

MeSH terms

  • Atherosclerosis* / complications
  • Atherosclerosis* / genetics
  • Gene Regulatory Networks
  • Humans
  • Ischemic Stroke*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcriptome / genetics

Substances

  • RNA, Long Noncoding