The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats

Ding, Xin; Sun, Bin; Huang, Jian; Xu, Lixiao; Pan, Jian; Chen, Fang; Tao, Yanfang; Hu, Shukun; Li, Ronghu; Han, Xiang; Miao, Po; Wang, Ying; Yu, Jian; Feng, Xing

doi:10.1016/j.neulet.2015.02.026

Cited by 58 publications

(32 citation statements)

References 33 publications

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“…Moreover, they were upregulated even in normoxic condition. There is evidence showing that miR-182 is also downregulated after hypoxia-ischemia brain injury in neonatal rats [65]. Jiang et al reported that miR-146a-5p could ameliorate ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6 in liver [12].…”

Section: Discussionmentioning

confidence: 99%

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O₂) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.

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Section: Discussionmentioning

confidence: 99%

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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“…We chose several published target genes of miR-182 and PTEN/AKT pathway to do Ingenuity Pathway Analysis (IPA) and found it was more related to cell morphology and nervous system development ( Supplementary Figures S4A,B ). MiR-182 plays important roles in the synaptic connectivity of photoreceptors and retinal regeneration (Lumayag et al, 2013), and a literature described that miR-182 plays a role in regulating CLOCK expression after hypoxia-ischemia brain injury (Ding et al, 2015). It is worthy of further investigation for the function of miR-182 and BCAT2 in neuron regeneration.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Lü

et al. 2017

Front. Cell. Neurosci.

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MicroRNAs are implicated in neuronal development and maturation. Neuronal maturation, including axon outgrowth and dendrite tree formation, is regulated by complex mechanisms and related to several neurodevelopmental disorders. We demonstrated that one neuron-enriched microRNA, microRNA-182 (miR-182), played a significant role in regulating neuronal axon outgrowth and dendrite tree formation. Overexpression of miR-182 promoted axon outgrowth and complexity of the dendrite tree while also increasing the expression of neurofilament-M and neurofilament-L, which provide structural support for neurite outgrowth. However, a reduction of miR-182 inhibited neurite outgrowth. Furthermore, we showed that miR-182 activated the AKT pathway by increasing AKT phosphorylation on S473 and T308 and inhibiting PTEN activity by increasing phosphorylation on S380. Inhibition of AKT activity with the PI3-K inhibitor LY294002 could downregulate AKT and PTEN phosphorylation and suppress axon outgrowth. In addition, we showed that BCAT2 might be the target of miR-182 that takes part in the regulation of neuronal maturation; blockage of endogenous BCAT2 promotes axon outgrowth and AKT activity. These observations indicate that miR-182 regulates axon outgrowth and dendrite maturation involving activation of the PTEN/AKT pathway.

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“…4 needle was used to suture the incision. The neonatal mice were placed back with the female mice for 1 to 2 h after the operation [17, 19]. Then, the mice were put into a sealed, 50-mL low-oxygen container at a constant temperature of 20 °C after they were fully awake.…”

Section: Methodsmentioning

confidence: 99%

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

Sun

Guo

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. Methods: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. Results: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. Conclusions: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

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The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats

Cited by 58 publications

References 33 publications

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

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

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

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