Disruption of RIP1-FADD Complexes by MicroRNA-103/107 Provokes Necrotic Cardiac Cell Death

Dhingra, Rimpy; Lin, Junjun; Kirshenbaum, Lorrie A.

doi:10.1161/circresaha.115.307023

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…MicroRNAs take part in many important biological processes, including early embryonic development [ 12 ] and fat metabolism [ 13 ], and they even regulate the differentiation of stem cells [ 14 ]. However, the abnormal expression of miRNAs is closely related to the occurrence and development of human cancer (cell proliferation [ 15 ], apoptosis [ 16 ], and cell death [ 17 ]). MicroRNAs have been shown to play crucial roles in the development and progression of different kinds of cancer, including HCC [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.

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Section: Introductionmentioning

confidence: 99%

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

et al. 2021

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“…In the circRNA-based ceRNA regulatory network, some miRNAs and mRNAs directly regulate cardiac hypertrophy or cardiac fibrosis. Previous research has shown that miR-103-3p is negatively linked to cardiomyocyte fate ( Dhingra et al, 2015 ; Wang et al, 2015 ). Zhang et al indicated that overexpression of cytosolic long noncoding RNA cytb protects against pressure-overload-induced heart failure by sponging microRNA-103-3p ( Zhang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis

et al. 2022

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Cardiac hypertrophy initially serves as an adaptive response to physiological and pathological stimuli. Sustained hypertrophy progress to pathological cardiac hypertrophy, cardiac fibrosis and ultimately lead to heart failure, one of the leading medical causes of mortality worldwide. Intervention of pathological cardiac hypertrophy can effectively reduce the occurrence of heart failure. Abundant factors, such as adrenergic, angiotensin, and endothelin (ET-1) receptors, have been shown to participate in the regulation of pathological cardiac hypertrophy. Recently, an increasing number of studies have indicated that circRNA and circRNA-miRNA–mRNA network regulation is indispensable for the posttranscriptional regulation of mRNA in cardiac hypertrophy. In our study, the morphological, cardiac function and pathological changes during cardiac hypertrophy were investigated. RNA sequencing identified 93 circRNAs that were differentially expressed in the TAC_2w group, and 55 circRNAs in the TAC_4w group compared with the sham group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified several significant pathways, including hypertrophic cardiomyopathy, extracellular matrix (ECM)-receptor interaction and focal adhesion. Coexpression analyses were performed for differentially expressed circRNAs and differentially expressed mRNAs. Based on gene set enrichment analysis (GSEA), 8 circRNAs (mmu-Nfkb1_0001, mmu-Smad4_0007, mmu-Hecw2_0009, mmu-Itgbl1_0002, mmu-Lrrc2_0005, mmu-Cpeb3_0007, mmu-Ryr2_0040, and mmu-Rtn4_0001) involved in cardiac hypertrophy and cardiac fibrosis were identified. We validated some key circRNAs by qPCR. The crucial coexpression of circRNA–mRNA and its interaction with miRNA showed the possible mechanism of circRNAs in the process of cardiac dysfunction. Our results may provide promising targets for the treatment of pathological cardiac hypertrophy and fibrosis.

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“…miR-155 represses cardiomyocyte progenitor cell necroptosis by targeting RIP1 rather than activating the Akt pro-survival pathway (96), suggesting that miR-155 might be a novel approach in improving cell engraftment. Additionally, in a myocardial ischemia/reperfusion model, it was demonstrated that miR-103/107, as a necrosis-suppressor miRNA, directly targeted FADD (97,98). FADD participates in hydrogen peroxide-induced necroptosis by influencing the formation of RIP1/RIP3 complex, suggesting that FADD-targeting by miR-103/107 might be a new approach for preventing myocardial necrosis.…”

Section: Rip1/rip3 Inhibition In Necroptosismentioning

confidence: 99%

RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review)

et al. 2019

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Necroptosis is a type of programmed cell death with necrotic morphology, occurring in a variety of biological processes, including inflammation, immune response, embryonic development and metabolic abnormalities. The current nomenclature defines necroptosis as cell death mediated by signal transduction from receptor-interacting serine/threonine kinase (RIP) 1 to RIP3 (hereafter called RIP1/RIP3). However, RIP3-dependent cell death would be a more precise definition of necroptosis. RIP3 is indispensable for necroptosis, while RIP1 is not consistently involved in the signal transduction. Notably, deletion of RIP1 even promotes RIP3-mediated necroptosis under certain conditions. Necroptosis was previously thought as an alternate process of cell death in case of apoptosis inhibition. Currently, necroptosis is recognized to serve a pivotal role in regulating various physiological processes. Of note, it mediates a variety of human diseases, such as ischemic brain injury, immune system disorders and cancer. Targeting and inhibiting necroptosis, therefore, has the potential to be used for therapeutic purposes. To date, research has elucidated the suppression of RIP1/RIP3 via effective inhibitors and highlighted their potential application in disease therapy. The present review focused on the molecular mechanisms of RIP1/RIP3-mediated necroptosis, explored the functions of RIP1/RIP3 in necroptosis, discussed their potential as a novel therapeutic target for disease therapy, and provided valuable suggestions for further study in this field.

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Disruption of RIP1-FADD Complexes by MicroRNA-103/107 Provokes Necrotic Cardiac Cell Death

Cited by 6 publications

References 9 publications

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis

RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review)

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