Radiation induced transcriptional and post-transcriptional regulation of the hsa-miR-23a ~ 27a ~ 24-2 cluster suppresses apoptosis by stabilizing XIAP

Heider, Theresa; Mutschelknaus, Lisa; Radulović, Vanja; Winkler, Klaudia; Kimmel, Julia; Anastasov, Nataša; Atkinson, Michael J.; Moertl, Simone

doi:10.1016/j.bbagrm.2017.08.006

Cited by 13 publications

(8 citation statements)

References 78 publications

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“…It has been determined that the miR-23a~27a~24-2 cluster takes part in the regulation of endothelial cell apoptosis [32], osteoblast differentiation [33], neuronal apoptosis [34], and erythropoiesis [35]. During the differentiation of bovine adipocyte progenitor cells and 3T3-L1 cells, miR-23a serves as a negative regulator [20,36].…”

Section: The Mir-23a~27a~24-2 Clustermentioning

confidence: 99%

The Role of MicroRNAs in Muscle Tissue Development in Beef Cattle

Raza

Kaster

Khan

et al. 2020

Genes

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In this review, we highlight information on microRNA (miRNA) identification and functional characterization in the beef for muscle and carcass composition traits, with an emphasis on Qinchuan beef cattle, and discuss the current challenges and future directions for the use of miRNA as a biomarker in cattle for breeding programs to improve meat quality and carcass traits. MicroRNAs are endogenous and non-coding RNA that have the function of making post-transcriptional modifications during the process of preadipocyte differentiation in mammals. Many studies claim that diverse miRNAs have an impact on adipogenesis. Furthermore, their target genes are associated with every phase of adipocyte differentiation. It has been confirmed that, during adipogenesis, several miRNAs are differentially expressed, including miR-204, miR-224, and miR-33. The development of mammalian skeletal muscle is sequentially controlled by somite commitment into progenitor cells, followed by their fusion and migration, the proliferation of myoblasts, and final modification into fast- and slow-twitch muscle fibers. It has been reported that miRNA in the bovine MEG3-DIO3 locus has a regulatory function for myoblast differentiation. Likewise, miR-224 has been associated with controlling the differentiation of bovine adipocytes by targeting lipoprotein lipase. Through the posttranscriptional downregulation of KLF6, miR-148a-3p disrupts the proliferation of bovine myoblasts and stimulates apoptosis while the miR-23a~27a~24-2 cluster represses adipogenesis. Additional to influences on muscle and fat, bta-mir-182, bta-mir-183, and bta-mir-338 represent regulators of proteolysis in muscle, which influences meat tenderness.

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Section: The Mir-23a~27a~24-2 Clustermentioning

confidence: 99%

The Role of MicroRNAs in Muscle Tissue Development in Beef Cattle

Raza

Kaster

Khan

et al. 2020

Genes

View full text Add to dashboard Cite

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“…miR-23a, miR-451a and miR-101-3p are interesting candidates to contribute to suppressed apoptosis in endothelial recipient cells [51,52]. These miRNAs are decreased (miR-23a-3p, mir-451a) or increased (miR-101-3p) in EVs from irradiated donors, and corresponding regulations were previously shown to suppress apoptosis in endothelial cells [51,[53][54][55].…”

Section: Physiological Relevance Of Pbmc-derived Evs After Ionizing Radiationmentioning

confidence: 99%

Radiation Exposure of Peripheral Mononuclear Blood Cells Alters the Composition and Function of Secreted Extracellular Vesicles

Moertl

Buschmann

Azimzadeh

et al. 2020

IJMS

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Normal tissue toxicity is a dose-limiting factor in radiation therapy. Therefore, a detailed understanding of the normal tissue response to radiation is necessary to predict the risk of normal tissue toxicity and to development strategies for tissue protection. One component of normal tissue that is continuously exposed during therapeutic irradiation is the circulating population of peripheral blood mononuclear cells (PBMC). PBMCs are highly sensitive to ionizing radiation (IR); however, little is known about how IR affects the PBMC response on a systemic level. It was the aim of this study to investigate whether IR was capable to induce changes in the composition and function of extracellular vesicles (EVs) secreted from PBMCs after radiation exposure to different doses. Therefore, whole blood samples from healthy donors were exposed to X-ray radiation in the clinically relevant doses of 0, 0.1, 2 or 6 Gy and PBMC-secreted EVs were isolated 72 h later. Proteome and miRNome analysis of EVs as well as functional studies were performed. Secreted EVs showed a dose-dependent increase in the number of significantly deregulated proteins and microRNAs. For both, proteome and microRNA data, principal component analysis showed a dose-dependent separation of control and exposed groups. Integrated pathway analysis of the radiation-regulated EV proteins and microRNAs consistently predicted an association of deregulated molecules with apoptosis, cell death and survival. Functional studies identified endothelial cells as an efficient EV recipient system, in which irradiation of recipient cells further increased the uptake. Furthermore an apoptosis suppressive effect of EVs from irradiated PBMCs in endothelial recipient cells was detected. In summary, this study demonstrates that IR modifies the communication between PBMCs and endothelial cells. EVs from irradiated PBMC donors were identified as transmitters of protective signals to irradiated endothelial cells. Thus, these data may lead to the discovery of biomarker candidates for radiation dosimetry and even more importantly, they suggest EVs as a novel systemic communication pathway between irradiated normal, non-cancer tissues.

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“…However, the expression patterns and functions of the miRNAs in this cluster are not always the same and are even opposite depending on the cell type and biological process [12]. Studies have shown that the miR-23a~27a~24-2 cluster regulates endothelial cell apoptosis [13], osteoblast differentiation [14,15], neuronal apoptosis [16], and erythropoiesis [17]. Recent studies in humans have also indicated that the miR-23a~27a~24-2 cluster may also significantly affect adipogenesis because many of their predicted target genes are involved in multiple signaling pathways related to lipid metabolism [12].…”

Section: Introductionmentioning

confidence: 99%

Cooperative and Independent Functions of the miR-23a~27a~24-2 Cluster in Bovine Adipocyte Adipogenesis

Wang

Zhang

et al. 2018

IJMS

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The miR-23a~27a~24-2 cluster is an important regulator in cell metabolism. However, the cooperative and independent functions of this cluster in bovine adipocyte adipogenesis have not been elucidated. In this study, we found that expression of the miR-23a~27a~24-2 cluster was induced during adipogenesis and this cluster acted as a negative regulator of adipogenesis. miR-27a and miR-24-2 were shown to inhibit adipogenesis by directly targeting glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) and diacylglycerol O-acyltransferase 2 (DGAT2), both of which promoted adipogenesis. Meanwhile, miR-23a and miR-24-2 were shown to target decorin (DCN), glucose-6-phosphate dehydrogenase (G6PD), and lipoprotein lipase (LPL), all of which repressed adipogenesis in this study. Thus, the miR-23a~27a~24-2 cluster exhibits a non-canonical regulatory role in bovine adipocyte adipogenesis. To determine how the miR-23a~27a~24-2 cluster inhibits adipogenesis while targeting anti-adipogenic genes, we identified another target gene, fibroblast growth factor 11 (FGF11), a positive regulator of adipogenesis, that was commonly targeted by the entire miR-23a~27a~24-2 cluster. Our findings suggest that the miR-23a~27a~24-2 cluster fine-tunes the regulation of adipogenesis by targeting two types of genes with pro- or anti-adipogenic effects. This balanced regulatory role of miR-23a~27a~24-2 cluster finally repressed adipogenesis.

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Radiation induced transcriptional and post-transcriptional regulation of the hsa-miR-23a ~ 27a ~ 24-2 cluster suppresses apoptosis by stabilizing XIAP

Cited by 13 publications

References 78 publications

The Role of MicroRNAs in Muscle Tissue Development in Beef Cattle

The Role of MicroRNAs in Muscle Tissue Development in Beef Cattle

Radiation Exposure of Peripheral Mononuclear Blood Cells Alters the Composition and Function of Secreted Extracellular Vesicles

Cooperative and Independent Functions of the miR-23a~27a~24-2 Cluster in Bovine Adipocyte Adipogenesis

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