Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2

Ji, Yamei; Yang, Xin; Huixia, Su

doi:10.1016/j.biopha.2017.12.012

Cited by 16 publications

(8 citation statements)

References 53 publications

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“…It was found that following Dex treatment, cell viability was suppressed, whereas cell apoptosis was promoted in a time-dependent manner. Further investigations also confirmed that Dex treatment led to the downregulation of miR-375, a novel potential therapeutic target for asthma treatment ( 34 ).…”

Section: Discussionmentioning

confidence: 79%

Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

Zheng

Gao

2022

Int J Mol Med

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Airway epithelial cell (AEC) dysfunction has been proven to be involved in the pathogenesis of asthma, which may be induced by the use of dexamethasone (Dex). The altered expression of microRNAs (miRNAs/miRs) has been found in asthma. However, the detailed mechanisms responsible for the effects of miR-375 on Dex-induced AEC dysfunction remain elusive. Thus, the present study aimed to elucidate these mechanisms. Following treatment with Dex for 0, 6, 12 and 24 h, AEC viability, migration, invasion and apoptosis were examined using Cell Counting Kit-8 (CCK-8), wound healing and Transwell assays, and flow cytometry, respectively. The expression levels of miR-375, dual specificity phosphatase 6 (DUSP6) and apoptosis-related proteins (Bcl-2, Bax, cleaved caspase-3) were measured using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The target genes and potential binding sites of miR-375 and DUSP6 were predicted using TargetScan and confirmed using dual-luciferase reporter assay. The viability, migration, invasion and apoptosis of Dex-treated AECs were further assessed with or without miR-375 and DUSP6. In the AECs (9HTE cells), Dex treatment suppressed cell viability and miR-375 expression, whereas it promoted cell apoptosis and the expression of DUSP6, the target gene of miR-375. The overexpression of miR-375 reversed the effects of Dex treatment on miR-375 expression, cell viability, migration and invasion, and apoptosis-related protein expression; in turn, these effects were reversed by the overexpression of DUSP6, with the exception of miR-375 expression. On the whole, the present study demonstrates that the overexpression of miR-375 counteracts the effects of Dex treatment on AEC viability, migration, invasion and apoptosis by targeting DUSP6. Thus, it was suggested that the downregulated expression of miR-375 may be a therapeutic target for AEC dysfunction.

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Section: Discussionmentioning

confidence: 79%

Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

Zheng

Gao

2022

Int J Mol Med

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“…Although JAK2 could serve as a downstream molecule of miR-375, the regulatory effects of miR-375 on JAK2 has not always been consistent. It is reported miR-375 represses mRNA and protein expression of Jak2 in airway smooth muscle cells and nasal mucosa cells [ 21 , 22 ], implying that miR-375 induces the degradation of JAK2 mRNA to decrease its expression. However, only the protein levels of JAK2 are mitigated by miR-375, while miR-375 has no detectable effects on JAK2 mRNA expression in MGC-803 cells and GES-1 cells [ 14 , 23 ], implying that miR-375 depresses JAK2 expression via blocking its translation.…”

Section: Discussionmentioning

confidence: 99%

MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway

Gong

Han

Zhuang

et al. 2022

Aging

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Aberrant neovascularization in the retina is an important threat to vision and closely related to several retinal diseases, such as wet form of age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. However, the pathogenesis remains largely unknown. MicroRNAs (miRNAs) have been demonstrated to play critical regulatory roles in angiogenesis. Therefore, we aimed to identify the key miRNAs that regulate retinal neovascularization and elucidate the potential underlying mechanisms. In the present study, we performed RNA sequencing of microRNAs in the retina and found that miR-375 was significantly downregulated in the retina of oxygen-induced retinopathy mice. In retinal microvascular endothelial cells (RMECs), overexpression of miR-375 inhibited cell proliferation and angiogenesis. Conversely, inhibition of miR-375 had the opposite effects. Moreover, our results showed that miR-375 negatively regulated the protein expression of JAK2 by inhibiting its translation. The promoting effects of anti-miR-375 on cell proliferation and angiogenesis were attenuated by an inhibitor of STAT3. These results indicate that miR-375 mitigates cell proliferation and angiogenesis, at least in part, through the JAK2/STAT3 pathway in RMECs, which implies an important underlying mechanism of retinal angiogenesis and provides potential therapeutic targets for retinal microangiopathy.

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“…High miR-126 expression is found in the asthmatic mice’s lung tissues and in the serum exosomes of allergic asthma patients [ 25 ]. miR-375 suppresses PDGF-induced ASM cell multiplication and migration via modulating the JAK2/STAT3 signal transduction [ 26 ]; miR-638 restrains PDGF-BB-induced human ASM cell multiplication and migration by targeting cyclin D1 and NOR1 [ 27 ]. The current study validated that miR-30b-5p was a new regulator of ASM cells’ multiplication and migration.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-30b-5p promotes the proliferation and migration of human airway smooth muscle cells induced by platelet-derived growth factor by targeting phosphatase and tensin homolog deleted on chromosome ten

2021

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Dysfunction of airway smooth muscle (ASM) cells is crucial in asthma pathogenesis. Here, microRNA-30b-5p (miR-30b-5p)’s function and mechanism in ASM cells’ multiplication and migration were investigated. Microarray was utilized for identifying the differentially expressed miRNAs in the bronchial epithelial cells of the asthma patients and healthy controls. Platelet-derived growth factor (PDGF) was employed to treat ASM cells to establish an in-vitro asthma model. Quantitative real-time PCR (qRT-PCR) was conducted for detecting the expressions of miR-30b-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2ʹ-deoxyuridine (BrdU) assays were used for examining cell multiplication; Transwell assay was performed for detecting cell migration; cell cycle was analyzed through flow cytometry. The targeted relationship between PTEN and miR-30b-5p was verified using a dual-luciferase reporter gene assay. Western blot was used for detecting the expressions of phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), PTEN, PI3K, protein kinase B (AKT) and p-AKT in ASM cells. We demonstrated that, miR-30b-5p expression in the bronchial epithelial cells of asthmatic patients was up-regulated. It was also increased in PDGF-stimulated ASM cells. Transfection of miR-30b-5p mimics facilitated ASM cells’ multiplication, migration and cycle progression, while inhibiting miR-30b-5p had the opposite effect. Furthermore, miR-30b-5p could target PTEN to repress PTEN expression. PTEN overexpression attenuated the effect of miR-30b-5p on ASM cells. Moreover, miR-30b-5p overexpression facilitated the expression of p-PI3K and p-AKT in PDGF-stimulated ASM cells. Collectively, miR-30b-5p activates the PI3K/AKT pathway by targeting PTEN to facilitate PDGF-induced dysfunction of ASM cells.

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Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2

Cited by 16 publications

References 53 publications

Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway

MicroRNA-30b-5p promotes the proliferation and migration of human airway smooth muscle cells induced by platelet-derived growth factor by targeting phosphatase and tensin homolog deleted on chromosome ten

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