Dataset Information

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis.

ABSTRACT: Methamphetamine (METH) abuse can result in severe neurotoxicity, for which the mechanism is not yet clear. In the present study, we investigated the role of noncoding RNAs in METH-induced dopaminergic neurotoxicity, and analyzed the underlying mechanism using bioinformatic methods. We confirmed by flow cytometry that miR-129-1-3p is involved in promoting dopaminergic apoptosis under METH treatment and its role could be inhibited by a high concentration of circ_0015891. Also, we combined transcriptomic data with bioinformatics to explore the downstream mechanism of miR-129-1-3p regulation of METH-induced apoptosis, highlighted the potentially pivotal figure of response to nutrition. Further bioinformatic analysis of circ_0015891 was conducted as well and showed that circ_0015891 was the sponge of various microRNAs that effect apoptosis by different mechanisms. Collectively, we found a novel circ_0015891/miR-129-1-3p axis that may be a promising therapeutic target for METH-induced dopaminergic neurotoxicity.

SUBMITTER: Deng B

PROVIDER: S-EPMC9530452 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis.

Deng Bingpeng B Tang Xuan X Wang Yong Y

Frontiers in endocrinology 20220920

Methamphetamine (METH) abuse can result in severe neurotoxicity, for which the mechanism is not yet clear. In the present study, we investigated the role of noncoding RNAs in METH-induced dopaminergic neurotoxicity, and analyzed the underlying mechanism using bioinformatic methods. We confirmed by flow cytometry that miR-129-1-3p is involved in promoting dopaminergic apoptosis under METH treatment and its role could be inhibited by a high concentration of circ_0015891. Also, we combined transcri ...[more]

PMID: 36204112

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Project description:Radiation-induced central nervous system toxicity is a significant risk factor for patients receiving cancer radiotherapy. Surprisingly, the mechanisms responsible for the DNA damage-triggered neuronal cell death following irradiation have yet to be deciphered. Using primary cortical neuronal cultures in vitro, we demonstrated that X-ray exposure induces the mitochondrial pathway of intrinsic apoptosis and that miR-23a-3p plays a significant role in the regulation of this process. Primary cortical neurons exposed to irradiation show the activation of DNA-damage response pathways, including the sequential phosphorylation of ATM kinase, histone H2AX, and p53. This is followed by the p53-dependent up-regulation of the pro-apoptotic Bcl2 family molecules, including the BH3-only molecules PUMA, Noxa, and Bim, leading to mitochondrial outer membrane permeabilization (MOMP) and the release of cytochrome c, which activates caspase-dependent apoptosis. miR-23a-3p, a negative regulator of specific pro-apoptotic Bcl-2 family molecules, is rapidly decreased after neuronal irradiation. By increasing the degradation of PUMA and Noxa mRNAs in the RNA-induced silencing complex (RISC), the administration of the miR-23a-3p mimic inhibits the irradiation-induced up-regulation of Noxa and Puma. These changes result in an attenuation of apoptotic processes such as MOMP, the release of cytochrome c and caspases activation, and a reduction in neuronal cell death. The neuroprotective effects of miR-23a-3p administration may not only involve the direct inhibition of pro-apoptotic Bcl-2 molecules downstream of p53 but also include the attenuation of secondary DNA damage upstream of p53. Importantly, we demonstrated that brain irradiation in vivo results in the down-regulation of miR-23a-3p and the elevation of pro-apoptotic Bcl2-family molecules PUMA, Noxa, and Bax, not only broadly in the cortex and hippocampus, except for Bax, which was up-regulated only in the hippocampus but also selectively in isolated neuronal populations from the irradiated brain. Overall, our data suggest that miR-23a-3p down-regulation contributes to irradiation-induced intrinsic pathways of neuronal apoptosis. These regulated pathways of neurodegeneration may be the target of effective neuroprotective strategies using miR-23a-3p mimics to block their development and increase neuronal survival after irradiation.

Dataset Information

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis.

Publications

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis.

Similar Datasets

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