MicroRNA-193b-3p reduces oxidative stress and mitochondrial damage in rats with cerebral ischemia-reperfusion injury via the seven in absentia homolog 1/Jun N-terminal kinase pathway

Yang, Tianye; Ge, Keyou; Wang, Fanlin; Fan, Jingxian

doi:10.1080/21655979.2022.2036398

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Results obtained from this study illustrate the actions of miR-34a in the control of ROS balance and oxidative stress that are associated with enhanced apoptosis. The latter was manifested by the lower levels of Bcl-xl and higher levels of activated/cleaved Caspase-3 and Caspase-7 as well as cleaved PARP, similar to recent findings on the effects of miR-193b-3p on oxidative stress and mitochondrial damage [ 68 ] as well as miR-506 on mitochondrial apoptosis [ 69 ]. In addition, miR-34a-5p has been shown to directly induce apoptosis through the regulation of some apoptosis genes, such as BCL-2 [ 16–18 ] and SIRT1 [ 13 ].…”

Section: Discussionsupporting

confidence: 87%

Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions

et al. 2022

Bioengineered

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Genome-derived microRNAs (miRNAs or miRs) control post-transcriptional gene expression critical for various cellular processes. Recently, we have invented a novel platform technology to achieve high-yield production of fully humanized, bioengineered miRNA agents (hBERAs) for research and development. This study is aimed to produce and utilize a new biologic miR-34a-5p (or miR-34a) molecule, namely, hBERA/miR-34a, to delineate the role of miR-34a-5p in the regulation of mitochondrial functions in human carcinoma cells. Bioengineered hBERA/miR-34a was produced through in vivo fermentation production and purified by anion exchange fast protein liquid chromatography. hEBRA/miR-34a was processed to target miR-34a-5p in human osteosarcoma and lung cancer cells, as determined by selective stem-loop reverse transcription quantitative polymerase chain reaction analysis. The mitochondrial inner membrane protein MPV17 like 2 ( MPV17L2 ) was validated as a direct target for miR-34a-5p by dual luciferase reporter assay. Western blot analysis revealed that bioengineered miR-34a-5p effectively reduced MPV17L2 protein outcomes, leading to much lower levels of respiratory chain Complex I activities and intracellular ATP that were determined with specific assay kits. Moreover, Seahorse Mito Stress Test assay was conducted, and the results showed that biologic miR-34a-5p sharply reduced cancer cell mitochondrial respiration capacity, accompanied by a remarkable increase of oxidative stress and elevated apoptotic cell death, which are manifested by greater levels of reactive oxygen species and selective apoptosis biomarkers, respectively. These results demonstrate the presence and involvement of the miR-34a-5p-MPV17L2 pathway in the control of mitochondrial functions in human carcinoma cells and support the utility of novel bioengineered miRNA molecules for functional studies.

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Section: Discussionsupporting

confidence: 87%

Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions

et al. 2022

Bioengineered

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“… 40 miR‐193b‐3p acts as a key player in the pathogenesis of cerebral ischemia–reperfusion injury, exerting neuroprotection through its ability to suppress neuronal apoptosis. 41 , 42 The current study unveiled a previously unreported phenomenon of diminished miR‐193b‐3p expression in the RVLM of SHRs. Elevated levels of miR‐193b‐3p in RVLM were found to suppress neuronal excitability and sympathetic outflow, leading to improved BP control.…”

Section: Discussionsupporting

confidence: 54%

miR‐193b‐3p and miR‐346 Exert Antihypertensive Effects in the Rostral Ventrolateral Medulla

Zhang,

Wang,

Dai

et al. 2024

JAHA

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Background Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological processes, but their influence on RVLM neuronal excitability and blood pressure (BP) remains widely unexplored. Methods and Results The RVLM miRNA profiles in spontaneously hypertensive rats were unveiled using RNA sequencing. Potential effects of these miRNAs in reducing neuronal excitability and BP and underlying mechanisms were investigated through various experiments. Six hundred thirty‐seven miRNAs were identified, and reduced levels of miR‐193b‐3p and miR‐346 were observed in the RVLM of spontaneously hypertensive rats. Increased miR‐193b‐3p and miR‐346 expression in RVLM lowered neuronal excitability, sympathetic outflow, and BP in spontaneously hypertensive rats. In contrast, suppressing miR‐193b‐3p and miR‐346 expression in RVLM increased neuronal excitability, sympathetic outflow, and BP in Wistar Kyoto and Sprague‐Dawley rats. Cdc42 guanine nucleotide exchange factor ( Arhgef9) was recognized as a target of miR‐193b‐3p. Overexpressing miR‐193b‐3p caused an evident decrease in Arhgef9 expression, resulting in the inhibition of neuronal apoptosis. By contrast, its downregulation produced the opposite effects. Importantly, the decrease in neuronal excitability, sympathetic outflow, and BP observed in spontaneously hypertensive rats due to miR‐193b‐3p overexpression was greatly counteracted by Arhgef9 upregulation. Conclusions miR‐193b‐3p and miR‐346 are newly identified factors in RVLM that hinder hypertension progression, and the miR‐193b‐3p/ Arhgef9 /apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.

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“…heme oxygenase 1 (HMOX1)-mediated neurogenesis after permanent IS in mice 59 . The absentia homolog 1/Jun N-terminal kinase pathway can reduce oxidative stress and mitochondrial damage in rats with cerebral ischemia-reperfusion injury 60 . HspBs, HspB1, and HspB5 may be most important in the neuronal stress response to ischemia/reperfusion injury in the brain and may be involved in neuroprotection 61 .…”

Section: Discussionmentioning

confidence: 99%

Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke

Zhang,

Liang,

Xiong

et al. 2024

Sci Rep

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Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein–protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS.

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MicroRNA-193b-3p reduces oxidative stress and mitochondrial damage in rats with cerebral ischemia-reperfusion injury via the seven in absentia homolog 1/Jun N-terminal kinase pathway

Cited by 8 publications

References 42 publications

Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions

Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions

miR‐193b‐3p and miR‐346 Exert Antihypertensive Effects in the Rostral Ventrolateral Medulla

Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke

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