LncRNA Rian reduces cardiomyocyte pyroptosis and alleviates myocardial ischemia–reperfusion injury by regulating by the miR-17-5p/CCND1 axis

Kang, Hui; Yu, Hui; Zeng, Ling; Ma, Hao; Cao, Ge

doi:10.1038/s41440-022-00884-6

Cited by 21 publications

(9 citation statements)

References 42 publications

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“…Taken together, these data provided the first functional evidence that miR-17-5p from ADSC-exos pivotally modulates TXNIP inflammasome activation in macrophages, suggesting exosomal miR-17-5p injection may become a future target for constraining the progression of AAA. What is noteworthy, miR-17-5p has been demonstrated to alleviates myocardial ischemia–reperfusion injury by regulating cell pyroptosis, which was a new paradigm of cell death for fighting against vascular diseases [ 42 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Jiang

et al. 2022

Stem Cell Res Ther

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Background Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. Methods ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Results The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3′-untranslated region (3’UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. Conclusion ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.

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Section: Discussionmentioning

confidence: 99%

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Jiang

et al. 2022

Stem Cell Res Ther

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“…To systemically explore the potential ceRNA mechanisms between these differentially expressed lncRNAs and Becn1, miRNAs bound with Becn1 and lncRNAs bound with miRNAs were predicted respectively by Starbase database, then the predicted lncRNAs were intersected with the differentially up-regulated lncRNAs to obtain lncRNA/miRNA/mRNA ceRNA network, the results showed there were Rian/mmu-miR-145a-5p/Becn1, Tug1/mmu-miR-145a-5p/Becn1, Malat1/mmu-miR-30e-5p/Becn1 and H19/mmu-miR-299a-3p/Becn1 axes respectively. There have been reported that lncRNA Rian, lncRNA Tug1, lncRNA Malat1 and lncRNA H19 all serve as ceRNA involved in multiple biological process, such as apoptosis ( Wu et al, 2020 ; Yao et al, 2020 ), ferroptosis ( Liang et al, 2022 ; Zhang et al, 2022 ) and pyroptosis ( Sun, Mao & Ji, 2021 ; Kang et al, 2022 ). Zhang and He reported that lncRNA Malat1/mmu-miR-30a/Becn1 was involved in myocardial infarction ( Zhang & He, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury

et al. 2023

PeerJ

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Background Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.

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“…. Studies have revealed that HSPA8 [262], HSP90AA1 [259], MYH9 [339], SORT1 [335], ACTA2 [307], SOX2 [773], SMAD4 [774], GATA2 [775], CCND1 [776], SPI1 [777] and SMARCA4 [778] plays a key role in cardiovascular diseases. The altered expression of HSPA8 [174], MYH9 [209], FLNA (filamin A) [444], SOX2 [779], GATA2 [780], EP300 [781] and SMARCA4 [782] plays a key role in the progression of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Diabetic patients are prone to diabetic kidney disease (DKD), which may cause cardiovascular damage, hypertension and obesity, and reduce quality of life. As a result, the life quality of patients was seriously reduced. However, the pathogenesis of diabetic kidney disease (DKD) has not been fully elucidated, and current treatments remain inadequate. Therefore, it is essential to explore the molecular mechanism of DKD and its complications. Next Generation Sequancing (GSE217709) dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were picked out by R software. Then Gene ontology (GO) and REACTOME pathway enrichment analysis were performed by g:Profiler database, protein-protein interaction (PPI) of DEGs was constructed by Human Integrated Protein-Protein Interaction rEference (HIPPIE) database . Module analysis was carried out by Cytoscape plug-in PEWCC. Subsequently, miRNA-hub gene regulatory network and TF- hub gene regulatory network were performed by miRNet database and NetworkAnalyst database. Finally, validation of hub genes was performed by receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. In total, 958 DEGs, including 479 up regulated and 479 down regulated genes, were identified. The GO and pathway enrichment changes of DEGs were mainly enriched in biological regulation, multicellular organismal process, signaling by GPCR and extracellular matrix organization. Ten hub genes (HSPA8, HSP90AA1, HSPA5, SDCBP, HSP90B1, VCAM1, MYH9, FLNA, MDFI and PML) associated with DKD and its complications were identified. Bioinformatics analysis is a useful tool to explore the molecular mechanism and pathogenesis of DKD and its complications. The identified hub genes may participate in the onset and development of DKD and its complications and serve as therapeutic targets.

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LncRNA Rian reduces cardiomyocyte pyroptosis and alleviates myocardial ischemia–reperfusion injury by regulating by the miR-17-5p/CCND1 axis

Cited by 21 publications

References 42 publications

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

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