miR‑187‑3p inhibitor attenuates cerebral ischemia/reperfusion injury by regulating Seipin‑mediated autophagic flux

Ren, Zhen; Xie, Peng; Lv, Ju; Hu, Yumei; Guan, Zhi‐Zhong; Chen, Ling; Yu, Wenbin

doi:10.3892/ijmm.2020.4642

Cited by 13 publications

(11 citation statements)

References 54 publications

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“…Hence, we selected miR-187-3p for subsequent validation, and found that CTS-mediated phenotypic alterations in HASMCs at least in part through regulating miR-187-3p expression. The function of miR-187-3p in cancer, reperfusion injury and sepsis has now been identified [ 53–56 ]. For example, overexpression of miR-187-3p attenuates ischemia-reperfusion-induced pain sensitivity by inhibiting the release of P2X7R and subsequently mature IL-1β in the mouse spinal cord [ 55 ] miR-187-3p inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting S100A4 [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p

Yang

Wei

et al. 2021

Bioengineered

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The cardiovascular is a system that contains extremely complex mechanical factors, in which the circulatory flow of blood has rich mechanical laws. Many studies have revealed that mechanical factors play a very important role in the process of revascularization. Hence, it is essential to investigate the mechanical factors in the process of revascularization in depth. A cyclic tensile strain (CTS) was applied to human aortic smooth muscle cells (HASMCs) at a frequency of 1 Hz and amplitudes of 5%, 10% and 15%, respectively. SmallRNA-seq was used to identify differentially expressed miRNAs (DE-miRNAs) responding to CTS in HASMCs. Starbase database predicted the target genes of DE-miRNAs. Metascape was applied for GO and KEGG pathway enrichment analysis and protein–protein interaction network construction. The proliferation and migration of CTS-treated HASMCs were significantly enhanced, and apoptosis were significantly reduced compared to the control group. SmallRNA-seq results demonstrated that 55, 16 and 16 DE-miRNAs were present in 5%, 10% and 15% CTS-treated HASMCs, respectively. Compared to controls, with miR-26a-2-3p and miR-187-3p being the intersection of these DE-miRNAs. Starbase database identified 189 common target genes for miR-26a-2-3p and miR-187-3p. Common target genes are mainly enriched in the basolateral plasma membrane and endocytosis. Further, in vitro experiments exhibited that CTS upregulated miR-187-3p expression, and miR-187-3p enhanced the proliferation and migration of HASMCs and reduced their apoptosis. It is suggested that miR-187-3p may be an important target for CTS participate in the process of cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p

Yang

Wei

et al. 2021

Bioengineered

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“…The role of seipin in diseases not caused by BSCL2 mutations has attracted more and more attention in recent years. At present, the relationships between seipin and metabolic [ 16 ], neurodegenerative [ 10 , 17 , 18 , 19 , 20 , 166 ], and other diseases [ 21 , 167 , 168 ] have been reported.…”

Section: Research Advances Acquired From Diseases Associated With Abn...mentioning

confidence: 99%

“…In glioblastoma patients and glioblastoma cell lines, the expression of BSCL2 is increased [ 167 ]. In ischaemia/reperfusion-induced cerebral damage, the expression of seipin is inhibited by elevated miR-187-3p (a microRNA which can bind to the protein-coding sequence of seipin), and suppression of seipin expression increases neuronal apoptosis via deficient autophagic flux and ER stress [ 18 , 19 ]. Furthermore, SKO mice have exacerbated neurological disorder and enlarged infarct size that may be caused by increased blood–brain barrier permeability, amplified ER stress, and elevated glucose levels, as well as decreased leptin and adiponectin levels [ 170 ].…”

Section: Research Advances Acquired From Diseases Associated With Abn...mentioning

confidence: 99%

“…Both CGL2 and PELD are inherited as autosomal recessive, whereas BSCL2 -associated motor neuron diseases are almost all autosomal dominant. Furthermore, the expression levels of seipin are found to be closely related with the progress of more common diseases not caused by BSCL2 mutations, implying that seipin may have potential prognostic and therapeutic values in these diseases [ 16 , 17 , 18 , 19 , 20 , 21 ]. In this review, we integrate the findings of these papers, exploring the expression, regulation, and function of seipin, aiming to provide fundamental insights into its critical role in the pathogenesis of human diseases and experimental animal models.…”

Section: Introductionmentioning

confidence: 99%

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Role of Seipin in Human Diseases and Experimental Animal Models

Yang

Peng

et al. 2022

Biomolecules

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Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia’s encephalopathy), and BSCL2-associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by BSCL2 gene mutations.

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“… 9 MiR-187-3p inhibitor attenuates cerebral I/R injury through modulating Seipin-mediated autophagic flux. 10 MiR-211 protects brain against I/R injury by suppressing cell apoptosis. 11 MiR-124-5p reduces ROS production and improves the inflammatory microenvironment to protect against cerebral I/R injury by targeting NOX2.…”

Section: Introductionmentioning

confidence: 99%

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Ren¹,

Wang²,

Guo³

2021

NDT

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Background MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear. Methods To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay. Results MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo. Conclusion Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.

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miR‑187‑3p inhibitor attenuates cerebral ischemia/reperfusion injury by regulating Seipin‑mediated autophagic flux

Cited by 13 publications

References 54 publications

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p

Role of Seipin in Human Diseases and Experimental Animal Models

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

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