MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway

Wang, Wu M.; Lü, Gang; Su, Xian; Lyu, Hao; Poon, Wai Sang

doi:10.3389/fncel.2017.00096

Cited by 25 publications

(21 citation statements)

References 55 publications

(62 reference statements)

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“… 32 A study in cortical neurons showed that miR-182-5p regulates neurite outgrowth via activation of the PI3K-Akt pathway. 33 Our results also show increased activation of the PI3K-Akt pathway after increase of miR-182-5p and miR-183-5p in PMNs, and a similar trend could be observed in NC siRNA-transfected cultures treated with GDNF. The importance of PI3K-Akt signaling was underlined by Akt inhibition in MPP + -treated cultures, diminishing the beneficial effects of both miRNAs and GDNF on DA neuron survival in PMN cultures.…”

Section: Discussionsupporting

confidence: 86%

miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons

Roser

Gomes

Halder

et al. 2018

Molecular Therapy - Nucleic Acids

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Parkinson’s disease (PD) is the second-most-frequent neurodegenerative disorder worldwide. One major hallmark of PD is the degeneration of dopaminergic (DA) neurons in the substantia nigra. Glial cell line-derived neurotrophic factor (GDNF) potently increases DA neuron survival in models of PD; however, the underlying mechanisms are incompletely understood. MicroRNAs (miRNAs) are small, non-coding RNAs that are important for post-transcriptional regulation of gene expression. Using small RNA sequencing, we show that GDNF specifically increases the expression of miR-182-5p and miR-183-5p in primary midbrain neurons (PMNs). Transfection of synthetic miR-182-5p and miR-183-5p mimics leads to increased neurite outgrowth and mediates neuroprotection of DA neurons in vitro and in vivo, mimicking GDNF effects. This is accompanied by decreased expression of FOXO3 and FOXO1 transcription factors and increased PI3K-Akt signaling. Inhibition of endogenous miR-182-5p or miR-183-5p in GDNF-treated PMNs attenuated the pro-DA effects of GDNF. These findings unveil an unknown miR-mediated mechanism of GDNF action and suggest that targeting miRNAs is a new therapeutic avenue to PD phenotypes.

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Section: Discussionsupporting

confidence: 86%

miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons

Roser

Gomes

Halder

et al. 2018

Molecular Therapy - Nucleic Acids

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“…Which factor might be the direct target gene of miR-182-5p and interacted with the expression of PTEN still need further investigations. Previous study reported that miR-182 could activate AKT by inhibiting PTEN activity to promote axon outgrowth [41]. Another study showed that miR-182-5p down-regulated PTEN expression to protect H9c2 cells from hypoxia-induced apoptosis [24].…”

Section: Discussionmentioning

confidence: 99%

Ganoderic Acid A Protects Rat H9c2 Cardiomyocytes from Hypoxia-Induced Injury via Up-Regulating miR-182-5p

Zhang¹,

Chu²,

Liu³

2018

Cell Physiol Biochem

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Background/Aims: Ganoderic acid A (GAA) isolated from Ganoderma lucidum, shows various benefit activities, such as anti-tumor activity, anti-HIV activity and hepatoprotective activity. However, the potential effects of GAA on hypoxia-induced injury of cardiomyocytes are still unclear. In this study, we aimed to reveal the effects of GAA on hypoxic-induced H9c2 cell injury, as well as potential underlying molecular mechanisms. Methods: Rat H9c2 cardiomyocytes were cultured in hypoxia condition with different doses of GAA. Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. qRT-PCR was performed to assess the expression levels of microRNA-182-5p (miR-182-5p) and phosphatase and tensin homologue (PTEN). Cell transfection was conducted to change the expression levels of miR-182-5p and PTEN in H9c2 cells. Finally, protein levels of key factors involved in cell proliferation, cell apoptosis and PTEN/PI3K/AKT pathway were evaluated using western blotting. Results: Hypoxia treatment significantly induced H9c2 cell viability loss and apoptosis. GAA incubation remarkably protected H9c2 cells from hypoxia-induced viability loss, proliferation inhibition and apoptosis. In addition, GAA obviously enhanced the expression level of miR-182-5p in H9c2 cells. Suppression of miR-182-5p notably alleviated the protective effects of GAA on hypoxia-treated H9c2 cells. Furthermore, miR-182-5p negatively regulated the mRNA and protein levels of PTEN in H9c2 cells. GAA attenuated hypoxia-induced inactivation of PI3K/AKT pathway in H9c2 cells by up-regulating miR-182-5p and then down-regulating PTEN. Conclusion: GAA protected rat H9c2 cardiomyocytes from hypoxia-induced injury might via up-regulating miR-182-5p, down-regulating PTEN and then activating PI3K/AKT signaling pathway.

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“…Wang et al indicated that miR-182 could activate the AKT signaling pathway via increasing AKT phosphorylation. 39 Liu et al found that overexpression of miR-182 could promote the chemoresistance of colorectal cancer cells through activation of PI3K/AKT signaling pathway. 40 Cao et al revealed that miR-182 promote the proliferation and invasion of hepatocellular carcinoma cells via activating AKT/FOXO3a pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>LOC441178 Overexpression Inhibits the Proliferation and Migration of Esophageal Carcinoma Cells via Methylation of miR-182</p>

Chen

et al. 2020

OTT

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Background Long noncoding RNAs (lncRNAs) have been shown to play an important role in the development and progression of esophageal carcinoma (EC). Recently, lncRNA LOC441178 was shown to be dysregulated in many cancer types; however, the role of LOC441178 in EC remains unclear. Materials and Methods Flow cytometry, transwell and wound healing assays were used to measure the apoptosis and migration in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR was used to detect the level of miR-182 in LOC441178-overexpressed EC cells. In addition, DNA methylation status of miR-182 promoter in LOC441178-overexpressed ESCC cells was detected by methylation-specific PCR (MSP) and bisulfite sequencing PCR. Results In this study, we found that LOC441178 negatively regulated miR-182 expression in ESCC cells. In addition, overexpression of LOC441178 inhibited the proliferation and migration and induced apoptosis in ESCC cells via downregulation of miR-182. Moreover, overexpression of LOC441178 markedly inhibited the phosphorylation of Akt and phosphorylation FOXO3a and increased the expression of FOXO3a in ESCC cells via downregulation of miR-182. Mechanistically, LOC441178 overexpression epigenetically suppressed miR-182 expression via DNA methylation. In vivo experiments revealed that overexpression of LOC441178 inhibited ESCC tumor growth in mouse xenograft model. Conclusion Collectively, our data suggested that LOC441178 overexpression epigenetically inhibited tumorigenesis of ESCC via DNA methylation of miR-182. These data indicated that the LOC441178/miR-182 axis might represent a novel therapeutic option for the treatment of ESCC.

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MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway

Cited by 25 publications

References 55 publications

miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons

miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons

Ganoderic Acid A Protects Rat H9c2 Cardiomyocytes from Hypoxia-Induced Injury via Up-Regulating miR-182-5p

<p>LOC441178 Overexpression Inhibits the Proliferation and Migration of Esophageal Carcinoma Cells via Methylation of miR-182</p>

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