RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

Su, Qiang; Xu, Yu; Cai, Ruping; Dai, Rixin; Yang, Xiheng; Liu, Yang; Kong, Biao

doi:10.1016/j.omtn.2021.01.034

Cited by 24 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several miRNAs have been reported to regulate the redox system [6]. Among these, miR-146a is reported as a negative regulator of many cardiovascular diseases, such as myocardial infarction, doxorubicin-induced cardiotoxicity, and cardiac fibrosis in a constrictive pericarditis model [7][8][9]. Studies have described that miR-146a negatively regulates ROS 7 Oxidative Medicine and Cellular Longevity generation in H9c2 cardiomyocytes [18].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

miRNA‐146a Mimic Inhibits NOX4/P38 Signalling to Ameliorate Mouse Myocardial Ischaemia Reperfusion (I/R) Injury

Xiao

Ren

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Evidence suggests that miR-146a is implicated in the pathogenesis of cardiovascular diseases; however, the role of miR-146a in myocardial ischaemia reperfusion (I/R) injury is unclear. The aim of this study was to explore the functional role of miR-146a in myocardial ischaemia reperfusion injury and the underlying mechanism. C57BL/6J mice were subjected to 45 min of ischaemia and 1 week of reperfusion to establish a myocardial I/R injury model. A miR-146a mimic (0.5 mg/kg) was administered intravenously at the beginning of the ischaemia process. Neonatal rat cardiomyocytes were also subjected to hypoxia/reperfusion (H/R). Cells were treated with the miR-146a mimic or antagonist. As a result, the miR-146a mimic attenuated H/R-induced cardiomyocyte injury, as evidenced by increased cell viability and reduced lactate dehydrogenase (LDH) levels. In addition, the miR-146a mimic inhibited oxidative stress in cells suffering from H/R injury. Moreover, the miR-146a antagonist exerted adverse effects in vitro. In mice with myocardial I/R injury, the miR-146a mimic preserved cardiac function and reduced the infarction area and fibrosis. Moreover, the miR-146a mimic decreased the inflammatory response and reactive oxygen species (ROS) accumulation in mouse hearts. Mechanistically, we found that miR-146a directly regulated the transcription of NOX4, which subsequently affected P38 signalling in cardiomyocytes. When we knocked down NOX4, the effects of the miR-146a antagonist in worsening the cell condition were counteracted in in vitro experiments. Taken together, the results suggest that miR-146a protects against myocardial ischaemia reperfusion injury by inhibiting NOX4 signalling. The miR-146a mimic may become a potential therapeutic approach for patients with myocardial ischaemia reperfusion.

show abstract

Section: Discussionmentioning

confidence: 99%

“…miR-146a has been widely recognized as a critical regulatory element in the cardiovascular system. miR-146a was reported to regulate mitochondrial function in a myocardial infarction mouse model [ 7 , 8 ]. miR-146a also protected against myocardial fibrosis in a rat constrictive pericarditis model [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

miRNA‐146a Mimic Inhibits NOX4/P38 Signalling to Ameliorate Mouse Myocardial Ischaemia Reperfusion (I/R) Injury

Xiao

Ren

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Indeed, miR-146a, which is particularly enriched in the mitochondrial fraction of cardiomyocytes, exerts a cardioprotective role by inhibiting the mitochondria-dependent apoptotic pathway and attenuating the loss of mitochondrial membrane potential. Evidence from cardiomyocyte-specific knockout and overexpression experiments supported the hypothesis that adequate miR-146a levels are required to reduce the extent of myocardial infarction and cardiac dysfunction following ischemia/reperfusion damage ( Su et al, 2021 ). Notably, acute cellular damage can affect the trafficking of miRNAs between the mitochondrial and cytosolic compartments.…”

Section: Senescence-associated Mirnas Impact On Mitochondrial Functionmentioning

confidence: 98%

MicroRNAs as Factors in Bidirectional Crosstalk Between Mitochondria and the Nucleus During Cellular Senescence

et al. 2021

View full text Add to dashboard Cite

Mitochondria are essential organelles that generate most of the chemical energy to power the cell through ATP production, thus regulating cell homeostasis. Although mitochondria have their own independent genome, most of the mitochondrial proteins are encoded by nuclear genes. An extensive bidirectional communication network between mitochondria and the nucleus has been discovered, thus making them semi-autonomous organelles. The nucleus-to-mitochondria signaling pathway, called Anterograde Signaling Pathway can be deduced, since the majority of mitochondrial proteins are encoded in the nucleus, less is known about the opposite pathway, the so-called mitochondria-to-nucleus retrograde signaling pathway. Several studies have demonstrated that non-coding RNAs are essential “messengers” of this communication between the nucleus and the mitochondria and that they might have a central role in the coordination of important mitochondrial biological processes. In particular, the finding of numerous miRNAs in mitochondria, also known as mitomiRs, enabled insights into their role in mitochondrial gene transcription. MitomiRs could act as important mediators of this complex crosstalk between the nucleus and the mitochondria. Mitochondrial homeostasis is critical for the physiological processes of the cell. Disruption at any stage in their metabolism, dynamics and bioenergetics could lead to the production of considerable amounts of reactive oxygen species and increased mitochondrial permeability, which are among the hallmarks of cellular senescence. Extensive changes in mitomiR expression and distribution have been demonstrated in senescent cells, those could possibly lead to an alteration in mitochondrial homeostasis. Here, we discuss the emerging putative roles of mitomiRs in the bidirectional communication pathways between mitochondria and the nucleus, with a focus on the senescence-associated mitomiRs.

show abstract

“…Another non-canonical function of miRNAs is associated with their non-canonical localization in the mitochondria ( Figure 2 f). Even if it is not clear how they translocate into the mitochondria, it has been hypothesized that certain nuclear-encoded miRNAs, such as miR-143 and miR-146a, which play antagonistic roles against cardiac dysfunction [ 101 ] and atherosclerosis [ 102 ], might require AGO2 for their shuttling into the mitochondria [ 103 ] ( Figure 2 f). As an example, nuclear miR-146a translocates into the mitochondria and regulates mitochondrial function and cardiomyocyte apoptosis, a function that is decreased during ischemic reperfusion (I/R) [ 101 ].…”

Section: Non-canonical Function Of Ncrnas In Cvdmentioning

confidence: 99%

A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases

Natarelli¹,

Weber

2022

Biomedicines

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) are among the top leading causes of mortality worldwide. Besides canonical environmental and genetic changes reported so far for CVDs, non-coding RNAs (ncRNAs) have emerged as key regulators of genetic and epigenetic mechanisms involved in CVD progression. High-throughput and sequencing data revealed that almost 80% of the total genome not only encodes for canonical ncRNAs, such as micro and long ncRNAs (miRNAs and lncRNAs), but also generates novel non-canonical sub-classes of ncRNAs, such as isomiRs and miRNA- and lncRNA-like RNAs. Moreover, recent studies reveal that canonical ncRNA sequences can influence the onset and evolution of CVD through novel “non-canonical” mechanisms. However, a debate exists over the real existence of these non-canonical ncRNAs and their concrete biochemical functions, with most of the dark genome being considered as “junk RNA”. In this review, we report on the ncRNAs with a scientifically validated canonical and non-canonical biogenesis. Moreover, we report on canonical ncRNAs that play a role in CVD through non-canonical mechanisms of action.

show abstract

RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

Cited by 24 publications

References 36 publications

miRNA‐146a Mimic Inhibits NOX4/P38 Signalling to Ameliorate Mouse Myocardial Ischaemia Reperfusion (I/R) Injury

miRNA‐146a Mimic Inhibits NOX4/P38 Signalling to Ameliorate Mouse Myocardial Ischaemia Reperfusion (I/R) Injury

MicroRNAs as Factors in Bidirectional Crosstalk Between Mitochondria and the Nucleus During Cellular Senescence

A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases

Contact Info

Product

Resources

About