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.
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Abbreviations
- AIIS:
-
Atherosclerosis-induced ischemic stroke
- BLVRB:
-
Biliverdin reductase B
- CTA:
-
CT angiography
- delncRNAs:
-
Differentially expressed lncRNAs
- demRNAs:
-
Differentially expressed mRNAs
- GO:
-
Geneontology
- HECTD1:
-
HECT domain E3 ubiquitin protein ligase 1
- ICA:
-
Intracranial atherosclerosis
- KEGG:
-
Kyotoencyclopedia of genes and genomes
- lncRNAs:
-
Long non-coding RNAs
- MAT2A:
-
Methionine adenosyltransferase 2A
- MCAO:
-
Middle cerebral artery occlusion
- MRA:
-
Magnetic resonance angiography
- MRI:
-
Magnetic resonance imaging
- ncRNAs:
-
Non-coding RNAs
- OGD:
-
Oxygen and glucose deprivation
- ox-LDL:
-
Oxidized low-density lipoprotein
- qRT-PCR:
-
Real-time quantitative polymerase chain reaction
- SLC38A2:
-
Solute carrier family 38 member 2
- VPS13B:
-
Vacuolar protein sorting 13 homolog B
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Funding
This study was supported by grants from the National Natural Science Foundation of China (81571134, 81973512), the Natural Science Foundation of Jiangsu Province (BK20160032), the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology), Zhejiang Chinese Medical University (No. ZYAOX2018001), and Double First-Class Project of China Pharmaceutical University (CPU2018GY06, CPU2018GY20). This work was also supported by the Six Talent Peaks Project of Jiangsu Province to Tao Pang.
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All authors listed contributed immensely to this study. WR and JW performed the experiments and wrote the paper. WR, JW, JS, and YJ collected the samples, performed molecular biology experiments, in vitro experiments, and analyzed the data. TP and JL designed the research, discussed the results, and reviewed the manuscript.
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Ruan, W., Wu, J., Su, J. et al. Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke. Cell Mol Neurobiol 42, 265–278 (2022). https://doi.org/10.1007/s10571-020-00918-y
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DOI: https://doi.org/10.1007/s10571-020-00918-y