Abstract
Objectives
Ischemic stroke causes high morbidity, mortality and health burden in the world. MiR-342-5p
was associated with Alzheimer's disease and cardio-protection. Herein, we aimed to
reveal effects of miR-342-5p on cerebral ischemia injury as well as novel targets
for stroke.
Materials and methods
AgomiR-342-5p was intracerebroventricularly injected into the middle cerebral artery
occlusion (MCAO) mouse models to evaluate functions of miR-342-5p on cerebral ischemia.
RT-qPCR and western blot assays were used to evaluate genes expression. Oxygen-glucose
deprivation (OGD) was used as an in vitro model for ischemia. Viability and apoptosis ratio of neurons was evaluated by CCK-8,
LDH release detection, and flow cytometry. The potential targets of miR-342-5p were
predicted by Targetscan, and their interaction was confirmed by luciferase assay.
Results
The intervention of miR-342-5p effectively attenuated ischemic injury in MCAO mice.
MiR-342-5p overexpression could protect neurons against OGD-induced injury, as revealed
by increased cell viability and BCL2 expression, and decreased LDH release, apoptosis
ratio, and BAX expression in OGD-induced neurons. Mechanically, miR-342-5p could directly
bound with CCAR2 to inhibit its expression. Overexpressing CARR2 aggravated the OGD-induced
injury of neurons, which was partly restrained by overexpressing miR-342-5p reversed.
Furthermore, miR-342-5p/CARR2 axis regulates Akt/NF-κB signaling pathway in vitro as well as in vivo cerebral ischemia models.
Conclusions
MiR-342-5p inhibited neuron apoptosis by regulating Akt/NF-kB signaling pathway via
CCAR2 suppression. Our findings revealed the neuroprotection of miR-342-5p in cerebral
ischemia.
Keywords
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Reference
- microRNAs in cerebrovascular disease.Adv Exp Med Biol. 2015; 888: 155-195
- Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016.N Engl J Med. 2018; 379: 2429-2437
- E-selectin deficiency attenuates brain ischemia in mice.CNS Neurosci Ther. 2012; 18: 903-908
- The immunology of stroke: from mechanisms to translation.Nat Med. 2011; 17: 796-808
- Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal Transduct Target Ther. 2022; 7: 215
- The widespread regulation of microRNA biogenesis, function and decay.Nat Rev Genet. 2010; 11: 597-610
- Reexamining assumptions about miRNA-guided gene silencing.Nucleic Acids Res. 2022; 50: 617-634
- Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma.Theranostics. 2020; 10: 5209-5224
- The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis.J Hepatol. 2016; 64: 1378-1387
- miR-155 in cancer drug resistance and as target for miRNA-based therapeutics.Cancer Metastasis Rev. 2018; 37: 33-44
- Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity.Cell Res. 2017; 27: 882-897
- The role of MiR-132 in regulating neural stem cell proliferation, differentiation and neuronal maturation.Cell Physiol Biochem. 2018; 47: 2319-2330
- Electroacupuncture improves neurobehavioral function through targeting of SOX2-mediated axonal regeneration by MicroRNA-132 after ischemic stroke.Front Mol Neurosci. 2018; 11: 471
- Association between physical exercise and stroke recurrence among first-ever ischemic stroke survivors.Sci Rep. 2021; 11: 13372
- Longterm exercise-derived exosomal miR-342-5p: a novel exerkine for cardioprotection.Circ Res. 2019; 124: 1386-1400
- Reduced levels of miR-342-5p in plasma are associated with worse cognitive evolution in patients with mild Alzheimer's disease.Front Aging Neurosci. 2021; 13705989
- miR-342-5p decreases ankyrin G levels in Alzheimer's disease transgenic mouse models.Cell Rep. 2014; 6: 264-270
- Stroke, vascular dementia, and Alzheimer's disease: molecular links.J Alzheimers Dis. 2016; 54: 427-443
- Homocysteine enhances neural stem cell autophagy in in vivo and in vitro model of ischemic stroke.Cell Death Dis. 2019; 10: 561
- Endothelin-1-mediated cerebral ischemia in mice: early cellular events and the role of caspase-3.Apoptosis. 2019; 24: 578-595
- Progesterone enhances functional recovery after middle cerebral artery occlusion in male mice.J Cereb Blood Flow Metab. 2004; 24: 805-813
- MicroRNA-195 protection against focal cerebral ischemia by targeting CX3CR1.J Neurosurg. 2018; : 1-10
- Hypoxic-ischemic injury in neonatal brain: involvement of a novel neuronal molecule in neuronal cell death and potential target for neuroprotection.Int J Dev Neurosci. 2008; 26: 93-101
- Tumor suppressive role of miR-342-5p and miR-491-5p in human osteosarcoma cells.Pharmaceuticals (Basel). 2022; 15: 362
- Long non-coding RNA LINC00346 contributes to cisplatin resistance in nasopharyngeal carcinoma by repressing miR-342-5p.Open Biol. 2020; 10190286
- miR‑342‑5p promotes Zmpste24‑deficient mouse embryonic fibroblasts proliferation by suppressing GAS2.Mol Med Rep. 2017; 16: 8944-8952
- DBC1 regulates p53 stability via inhibition of CBP-dependent p53 polyubiquitination.Cell Rep. 2019; 26 (e4): 3323-3335
- A KDM4-DBC1-SIRT1 axis contributes to TGF-b induced mesenchymal transition of intestinal epithelial cells.Front Cell Dev Biol. 2021; 9697614
- DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage.J Mol Cell Biol. 2012; 4: 294-303
- CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/β-catenin-dependent transcriptional activation of SPARC.Biochem Biophys Res Commun. 2021; 580: 67-73
- DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.Oncogene. 2018; 37: 1326-1339
- CCAR2/DBC1 and Hsp60 positively regulate expression of survivin in neuroblastoma cells.Int J Mol Sci. 2019; 20: 131
- CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage.Oncotarget. 2015; 6: 17817-17831
- Mitochondrial CCAR2/DBC1 is required for cell survival against rotenone-induced mitochondrial stress.Biochem Biophys Res Commun. 2017; 485: 782-789
- A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation.Cell Death Dis. 2016; 7: e2453
- PI3K/Akt and apoptosis: size matters.Oncogene. 2003; 22: 8983-8998
- To be, or not to be: NF-kappaB is the answer–role of Rel/NF-kappaB in the regulation of apoptosis.Oncogene. 2003; 22: 8961-8982
- bFGF inhibits ER stress induced by ischemic oxidative injury via activation of the PI3K/Akt and ERK1/2 pathways.Toxicol Lett. 2012; 212: 137-146
- NF-kappaB signalling in cerebral ischaemia.Biochem Soc Trans. 2006; 34: 1291-1294
- SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1 via DBC1/SIRT1 axis.Oncogene. 2019; 38: 345-359
- DCAF12 promotes apoptosis and inhibits NF-κB activation by acting as an endogenous antagonist of IAPs.Oncogene. 2022; 41: 3000-3010
- Nrf2 Activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells.Mol Immunol. 2022; 148: 54-67
- DBC1 promotes anoikis resistance of gastric cancer cells by regulating NF-κB activity.Oncol Rep. 2015; 34: 843-849
- DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity.J Immunol. 2014; 193: 5515-5524
- Regulation of anoikis by deleted in breast cancer-1 (DBC1) through NF-κB.Apoptosis. 2013; 18: 949-962
Article info
Publication history
Published online: November 23, 2022
Accepted:
November 16,
2022
Received in revised form:
October 24,
2022
Received:
August 11,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106901
Copyright
© 2022 Elsevier Inc. All rights reserved.