MicroRNA-21 Modulates the Levels of Reactive Oxygen Species by Targeting SOD3 and TNFα

Zhang, Xiangming; Ng, Wooi Loon; Wang, Ping; Tian, Li; Werner, Erica; Wang, Huichen; Doetsch, Paul W.; Wang, Ya

doi:10.1158/0008-5472.can-12-0639

Cited by 165 publications

(120 citation statements)

References 20 publications

(25 reference statements)

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“…miRNAs also influence the ROS defense system. miR-21 inhibits the metabolism of superoxide to H 2 O 2 by directing attenuating SOD3 or by indirectly reducing SOD2 levels (208). In an epithelial cell line, miR-30b regulates ROS levels by targeting CATs (58).…”

Section: Protecting Mitochondrial Functionmentioning

confidence: 99%

The Use of microRNAs to Modulate Redox and Immune Response to Stroke

Ouyang

Stary

White

et al. 2015

Antioxidants & Redox Signaling

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Significance: Cerebral ischemia is a major cause of death and disability throughout the world, yet therapeutic options remain limited. The interplay between the cellular redox state and the immune response plays a critical role in determining the extent of neural cell injury after ischemia and reperfusion. Excessive amounts of reactive oxygen species (ROS) generated by mitochondria and other sources act both as triggers and effectors of inflammation. This review will focus on the interplay between these two mechanisms. Recent Advances: MicroRNAs (miRNAs) are important post-transcriptional regulators that interact with multiple target messenger RNAs coordinately regulating target genes, including those involved in controlling mitochondrial function, redox state, and inflammatory pathways. This review will focus on the regulation of mitochondria, ROS, and inflammation by miRNAs in the chain of deleterious intra-and intercellular events that lead to brain cell death after cerebral ischemia. Critical Issues: Although pretreatment using miRNAs was effective in cerebral ischemia in rodents, testing treatment after the onset of ischemia is an essential next step in the development of acute stroke treatment. In addition, miRNA formulation and delivery into the CNS remain a challenge in the clinical translation of miRNA therapy. Future Directions: Future research should focus on post-treatment and potential clinical use of miRNAs. Antioxid. Redox Signal. 22,[187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202]

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Section: Protecting Mitochondrial Functionmentioning

confidence: 99%

The Use of microRNAs to Modulate Redox and Immune Response to Stroke

Ouyang

Stary

White

et al. 2015

Antioxidants & Redox Signaling

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“…The resulting inhibition of VDAC reduces ion flux between the mitochondria and the cytosol, resulting in mitochondrial hyperpolarization and an increased threshold for the opening of the MPTP. Intriguingly, Zhang et al have demonstrated that miR-21 also modulates cellular ROS levels by targeting SOD2 and SOD3, the proteins which are responsible for reduction of more reactive free radical anion superoxide to the less reactive hydrogen peroxide (101). By promoting the accumulation of ROS, miR-21 up-regulation induces a cytosolic environment that mimics that which would occur after a period of hypoxia, while the additional role of miR-21 in MPTP regulation ensures that the cell is prepared to withstand such cytotoxic effects without succumbing to apoptosis.…”

Section: Targeting Mitochondrial Apoptosis Via the Akt/hk-ii Signalinmentioning

confidence: 99%

“…Nonetheless, all of these are potential contributors to the hypoxic program, and several have been shown to participate in metabolic regulation (Table 1). Furthermore, miRNA activity has been uncovered at nearly every level of the mitochondrial response to hypoxia, from HIF stabilization (9,32,46,88), to the induction of anaerobic glycolysis (44,53,55,82,101), to the suppression of oxidative phosphorylation (13,28,56,71). Thus, hypoxamirs represent key intermediaries between hypoxia, HIF, and the mitochondrial phenotype.…”

Section: Introductionmentioning

confidence: 99%

Hypoxamirs and Mitochondrial Metabolism

Cottrill

Chan²,

Loscalzo³

2014

Antioxidants & Redox Signaling

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Significance: Chronic hypoxia can drive maladaptive responses in numerous organ systems, leading to a multitude of chronic mammalian diseases. Oxygen homeostasis is intimately linked with mitochondrial metabolism, and dysfunction in these systems can combine to form the backbone of hypoxic-ischemic injury in multiple tissue beds. Increased appreciation of the crucial roles of hypoxia-associated miRNA (hypoxamirs) in metabolism adds a new dimension to our understanding of the regulation of hypoxia-induced disease. Recent Advances: Myriad factors related to glycolysis (e.g., aldolase A and hexokinase II), tricarboxylic acid cycle function (e.g., glutaminase and iron-sulfur cluster assembly protein 1/2), and apoptosis (e.g., p53) have been recently implicated as targets of hypoxamirs. In addition, several hypoxamirs have been implicated in the regulation of the master transcription factor of hypoxia, hypoxia-inducible factor-1a, clarifying how the cellular program of hypoxia is sustained and resolved. Critical Issues: Central to the discussion of metabolic change in hypoxia is the Warburg effect, a shift toward anaerobic metabolism that persists after normal oxygen levels have been restored. Many newly discovered targets of hypoxia-driven microRNA converge on pathways known to be involved in this pathological phenomenon and the apoptosis-resistant phenotype associated with it. Future Directions: The often synergistic functions of miRNA may make them ideal therapeutic targets. The use of antisense inhibitors is currently being considered in diseases in which hypoxia and metabolic dysregulation predominate. In addition, exploration of pleiotripic miRNA functions will likely continue to offer unique insights into the mechanistic relationships of their downstream target pathways and associated hypoxic phenotypes. Antioxid. Redox Signal. 21, 1189-1201.

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“…The oxidative stress response is a pathway which provides and activates several antioxidant proteins and enzymes such as glutathione or superoxide dismutase [42], both of which are directly regulated by different miRNAs to detoxify oxidative stress metabolites [47], [48]. Both, the heat stress response and the UPR are pathways meant to cope with the accumulation of misfolded proteins, mostly in the endoplasmic reticulum [40].…”

Section: Resultsmentioning

confidence: 99%

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva

2017

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MicroRNAs (miRNAs) play a central role in the regulation of many cellular processes including physiological and psychological stress reaction pathways. Psychological stress is an important factor for the genesis and maintenance of many diseases. Several miRNAs have already been described to be involved in its regulation. The presence of miRNAs in all body fluids implies a widespread role in communication throughout the whole organism and together with their stability makes them formidable candidates as biomarkers. Alterations of stress-associated miRNA expression levels have been found in the brain and whole blood of humans and animals. In this paper, we review the participation of miRNAs in stress-reactive processes as well as their usability as salivary biomarkers of such processes. In conclusion, we suggest that salivary miRNAs may be useful as noninvasive biomarkers to assess epigenetic regulation processes of chronic or acute psychological stress reactions.

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MicroRNA-21 Modulates the Levels of Reactive Oxygen Species by Targeting SOD3 and TNFα

Cited by 165 publications

References 20 publications

The Use of microRNAs to Modulate Redox and Immune Response to Stroke

The Use of microRNAs to Modulate Redox and Immune Response to Stroke

Hypoxamirs and Mitochondrial Metabolism

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva

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