A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies
Abstract
:1. Introduction
2. Methods and Inclusion Criteria
3. The Potential Diagnostic Value of Exosomal Noncoding RNAs in Ischemic Stroke
3.1. The Expression Profile of Exosomal Long Noncoding RNAs
3.2. The Expression Profile of Exosomal Circular RNAs
4. The Involvement of Exosomal Noncoding RNAs in the Pathophysiological Process of Ischemic Stroke
4.1. Exosomal Long Noncoding RNAs in the Process of Ischemic Stroke
4.1.1. Exosomal LncRNA RMRP
4.1.2. Exosomal LncRNA MALAT1
4.2. Exosomal Circular RNAs in the Process of Ischemic Stroke
4.2.1. Exosomal CircSHOC2
4.2.2. Exosomal CircRNA-0006896
4.2.3. Exosomal CircOGDH
4.2.4. Exosomal circ_0000647
4.2.5. Exosomal circFUNDC1
4.2.6. Exosomal CircAkap7
4.2.7. Exosomal Circ-Rps5
5. Recent Advances in Exosome Applications in the Treatment of Ischemic Stroke
6. Therapeutic Prospects of Exosomal Noncoding RNAs in the Treatment of Ischemic Stroke
7. Future Work and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Models and Tissues | Detection Method | Changes of Expression Profiles | Focal ncRNAs | Reference |
---|---|---|---|---|
Exosomes from peripheral serum in stroke patients | RNA-Seq and qRT-PCR | 1096 lncRNAs covering 307 showed elevated expression while 789 showed decline | lnc-CRKL-2 and lnc-NTRK3-4 ↑ RPS6KA2-AS1 and lnc-CALM1-7 ↓ | Xu [16] |
Exosomes from peripheral plasma in stroke patients | HTS and qRT-PCR | 1020 lncRNAs were differentially expressed, 226 lncRNAs increased and 794 lncRNAs decreased levels | Most: novel lnc_000288 ↑; novel lnc_000285 ↓ lnc_002015/hsa-mir342/PTPRC/AAMP; lnc001350/hsa-mir-3127/ST14 | Zhang [17] |
Exosomes from peripheral plasma in stroke patients | RNA-Seq and qRT-PCR | 319 lncRNAs including 97 increased expression and 222 showed reduction | lnc_000048, lnc_001350 and lnc_016442 ↑ lnc_002015 ↓ | Zhang [18] |
Exosomes from peripheral plasma in stroke patients | HTS | 3540 circRNAs, 1177 increased expression and 2363 decrease expression | / | Xu [19] |
Exosomes from peripheral plasma in stroke patients | RNA-Seq and qRT-PCR | 25 circRNAs, 9 circRNAs were significantly upregulated and 16 circRNAs were significantly downregulated | hsa_circ_0000698/hsa_circ_0002775/hsa_circ_0005585/hsa_circ_0043837 ↓; hsa-miR-16 ↑; VWF ↓; novel_circ_0010155 ↓; hsa-miR-939 ↑; septin 9 and MYLK2 ↓ | Xiao [20] |
Exosomes from peripheral plasma in stroke patients | RNA-Seq and qRT-PCR | 26 circRNAs, 7 circRNAs were significantly upregulated and 19 circRNAs were significantly downregulated | circ_0043837 circ_0001801 | Xiao [21] |
Source | RNA | Expression | Target/Mechanisms | Function/Effects of Dysregulation | References |
---|---|---|---|---|---|
Exosomes from HUVECs subjected to OGD | lncRNA RMRP | / | miR-206, miR-1-3p and RMRP/PI3K/Akt/mTOR pathway | Increased cell viability and decreased infarct volume by regulating apoptosis and inducing eNOS activation | Zhong [22] |
Exosomes from ischemic-preconditioned astrocytes | circSHOC2 | Upregulation | circSHOC2/miR-7670-3p/SIRT1 | Decreased infarct volume and neurobehavioral deficits by reducing neuronal apoptosis via regulating autophagy | Chen [23] |
Serum exosomes from patients with carotid plaque | circRNA-0006896 | Increased levels in UA group | circRNA-0006896-miR1264-DNMT1/SOCS3/JNK/STAT3 axis | Promoted endothelial cell migration and proliferation, induced plaque destabilization | Yan [24] |
Exosomes from ischemic mouse primary cortical neurons and plasma of AIS patients | CircOGDH | Upregulation | CircOGDH/miR-5112/COL4A4 | Knockdown relieved neuronal injury by inhibiting apoptosis The expression was positively related to the size of penumbra in AIS patients | Liu [25] |
Exosomes from OGD/R-induced SK-N-SH cells | circ_0000647 | Upregulation | circ_0000647/miR-126-5p/TRAF3 | Accelerate apoptosis, inflammation, oxidative stress and inhibit cell proliferation | Dai [26] |
Serum exosomes from AIS patients | circFUNDC1 | Upregulation | circFUNDC1/miR-375/PTEN | Knockdown promoted cell survival and angiogenesis | Bai [27] |
Exosomes from ADSCs | circAkap7 | / | circAkap7/miR-155-5p/ATG12, NRF2 | Protected against cerebral ischemic injury by promoting autophagy and inhibiting oxidative stress | Xu [28] |
Exosomes from ADSCs | cir_Rps5 | Upregulation | cir_Rps5/miR-124-3p/SIRT7 axis | Improved ischemic induced cognitive function via decreasing neuronal damage in the hippocampus | Yang [29] |
RVG-circSCMH1-EVs | circular RNA SCMH1 | / | circSCMH1/MeCP2/Mobp, Igfbp3, Fxyd1, and Prodh | Enhanced functional recovery including promotion of brain plasticity, reduced glial activation, and peripheral immune cell infiltration | Yang [30] |
RBP-Exo/AMO181a-chol | miR-181a | / | Bcl-2 | Decreased infarct volume by inhibiting inflammation and apoptosis | Kim [31] |
Origin | Cargo | Function | Target | Implication | Ref. |
---|---|---|---|---|---|
Neural progenitor cell | / | Inhibited NF-κB signaling pathway | ECs, astrocytes | Enhanced BBB integrity poststroke | Zhang [38] |
Mesenchymal stromal cell | Curcumin | Biochemically engineered cRGD-Exo | Microglia, neurons, astrocytes. | Inhibited inflammation and cellular apoptosis | Tian [46] |
Aqueous suspension | / | Constructed cl PGP-PEG-DGL/CAT-Aco NPs ROS-mediated apoptosis | Neuronal cells | Reduce infarct volume through suppressing inflammation | Zhang [47] |
Mesenchymal stem cell | Therapeutic growth factors | Constructed MSC-IONP-derived magnetic nanovesicles | ECs, neuronal cells, macrophages | Decreased infarction volume and improved motor function via angiogenesis, anti-inflammation and anti-apoptosis | Kim [48] |
Neural progenitor cell | MiRNAs | Constructed RGD-EV MAPK signal pathway | Microglia | Improved targeting ability to the ischemic lesion and suppressed poststroke inflammation | Tian [49] |
Neural stem cell | MiRNAs | Constructed IFN-γ-hNSC-Exo | Neurons, microglia | Reduced infarct volume and facilitated the neurological functional recovery by increasing cell proliferation and survival, decreasing cell apoptosis and inflammation | Zhang [50] |
Mesenchymal stromal cell | MiR-210 | Constructed RGD-Exo | ECs | Improved microvascular angiogenesis by upregulating VEGF expression | Zhang [51] |
HEK293T cells | HMGB1- siRNA | Constructed RVG-Exo | Neuro2A cells | Reduced infarct volume by suppressing TNF-α expression and cell apoptosis | Kim [52] |
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Wang, Q.; Chen, Y.; Meng, L.; Yin, J.; Wang, L.; Gong, T. A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies. Brain Sci. 2022, 12, 1000. https://doi.org/10.3390/brainsci12081000
Wang Q, Chen Y, Meng L, Yin J, Wang L, Gong T. A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies. Brain Sciences. 2022; 12(8):1000. https://doi.org/10.3390/brainsci12081000
Chicago/Turabian StyleWang, Qianwen, Yuhui Chen, Lingbing Meng, Jiawen Yin, Li Wang, and Tao Gong. 2022. "A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies" Brain Sciences 12, no. 8: 1000. https://doi.org/10.3390/brainsci12081000