MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating USP22-mediated Sirt1/JAK/STAT3 signaling.

MicroRNA-30e-5p (miR-30e-5p) is a tumor suppressor that is known to be downregulated in non-small cell lung cancer (NSCLC). However, how miR-30e-5p inhibits NSCLC tumorigenesis is not known. Ubiquitin-specific peptidase 22 (USP22) is upregulated in NSCLC and promotes tumorigenesis via a Sirt1-JAK-STAT3 pathway. In this study, we investigated whether miR-30e-5p inhibits tumor growth by targeting USP22 in NSCLC. Our results reveal that miR-30e-5p expression was correlated negatively with USP22 in NSCLC tissues. Luciferase reporter assays showed that miR-30e-5p negatively regulated USP22 expression by binding to a specific sequence in the 3'UTR. MiR-30e-5p overexpression and USP22 knockdown significantly inhibited tumor growth in vivo and induced cell cycle arrest and apoptosis in NSCLC cells in vitro. The effects of miR-30e-5p inhibition were prevented by USP22 knockdown. MiR-30e-5p inhibited SIRT1 expression and increased expression of p53 and the phosphorylated form of STAT3 (pSTAT3). Furthermore, miR-30e-5p prevented USP22-mediated regulation of SIRT1, pSTAT3, and p53 expression. Taken together, these findings suggest that miR-30e-5p suppresses NSCLC tumorigenesis by downregulatingUSP22-mediated Sirt1/JAK/STAT3 signaling. Our study has identified miR-30e-5p as a potential therapeutic target for the treatment of NSCLC.

Cross-modal missing time-series imputation using dense spatio-temporal transformer nets.

Due to irregular sampling or device failure, the data collected from sensor network has missing value, that is, missing time-series data occurs. To address this issue, many methods have been proposed to impute random or non-random missing data. However, the imputation accuracy of these methods are not accurate enough to be applied, especially in the case of complete data missing (CDM). Thus, we propose a cross-modal method to impute time-series missing data by dense spatio-temporal transformer nets (DSTTN). This model embeds spatial modal data into time-series data by stacked spatio-temporal transformer blocks and deployment of dense connections. It adopts cross-modal constraints, a graph Laplacian regularization term, to optimize model parameters. When the model is trained, it recovers missing data finally by an end-to-end imputation pipeline. Various baseline models are compared by sufficient experiments. Based on the experimental results, it is verified that DSTTN achieves state-of-the-art imputation performance in the cases of random and non-random missing. Especially, the proposed method provides a new solution to the CDM problem.

Long Noncoding RNA SNHG4 Attenuates the Injury of Myocardial Infarction via Regulating miR-148b-3p/DUSP1 Axis.

Objective: Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI. Methods: Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1ß, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships. Results: SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia. Conclusions: Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.

CircUBXN7 mitigates H/R-induced cell apoptosis and inflammatory response through the miR-622-MCL1 axis.

BACKGROUND: Hypoxia/reoxygenation (H/R)-mediated apoptosis and inflammation are major causes of tissue injury in acute myocardial infarction (AMI). Exploring the underlying mechanisms of cardiomyocyte injury induced by H/R is important for AMI treatment. Circular RNAs have been demonstrated to paly vital roles in the pathogenesis of AMI. Our study aimed to explore the function of circular RNA UBXN7 (circUBXN7) in regulating H/R-induced cardiomyocyte injury. METHODS: H/R-treated H9c2 cells and a mouse model of AMI were used to investigate the function of circUBXN7 in H/R damage and AMI. The expressions of circUNXN7, miR-622 and MCL1 were analyzed by RT-qPCR. CCK-8 was used for examining cell viability. Cell apoptosis was evaluated with caspase 3 activity and Annexin V/PI staining. MCL1, Bax, Bcl-2 and cleaved-caspase 3 were examined with western blot. ELISA was used to examine the secretion of IL-6, TNF-α and IL-1ß. RESULTS: CircUBXN7 was downregulated in patients and mice with AMI, as well as in H/R-treated cells. Overexpression of circUBXN7 mitigated H/R-mediated apoptosis and secretion of inflammatory factors including IL-6, TNF-α and IL-1ß. CircUBXN7 suppressed cell apoptosis and inflammatory reaction induced by H/R via targeting miR-622. MiR-622 targeted MCL1 to restrain its expression in H9c2 cells. Knockdown of MCL1 abrogated circUBXN7-mediated alleviation of apoptosis and inflammation after H/R treatment. CONCLUSION: CircUBXN7 mitigates cardiomyocyte apoptosis and inflammatory reaction in H/R injury by targeting miR-622 and maintaining MCL1 expression. Our study provides novel potential therapeutic targets for AMI treatment.

MicroRNA-15a inhibition protects against hypoxia/reoxygenation-induced apoptosis of cardiomyocytes by targeting mothers against decapentaplegic homolog 7.

Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in coronary heart disease and cardiac surgery, and is associated with aberrant microRNA (miR) expression. Previous studies have demonstrated that inhibition of miR-15a expression may ameliorate I/R­induced myocardial injury. In the present study, the potential role and underlying mechanism of miR­15a in hypoxia/reoxygenation­induced apoptosis of cardiomyocytes was investigated. Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by 24 h reoxygenation. Using recombinant lentivirus vectors, the inhibition of miR­15a was indicated to significantly reduce cardiomyocyte apoptosis and release of lactate dehydrogenase and malondialdehyde. Conversely, upregulated miR­15a expression was pro­apoptotic. Mothers against decapentaplegic homolog 7 (SMAD7) was identified by bioinformatics analysis as a potential target of miR­15a. Luciferase reporter assays and western blotting for endogenous SMAD7 protein indicated that miR­15a inhibited SMAD7 expression via its 3'­untranslated region. Nuclear levels of nuclear factor­κB (NF­κB) p65 were increased by miR­15a expression and decreased by miR­15a inhibition, which is consistent with the possibility that the inhibition of SMAD7 by miR-15a results in NF­κB activation. These findings suggested that the therapeutic effects of miR­15a inhibition on I/R injury may potentially be explained by its ability to release SMAD­7­dependent NF­κB inhibition. This may provide evidence for miR­15a as a potential therapeutic target for the treatment of cardiac I/R injury.

Coarctation of the aorta associated with agenesis of left common carotid artery and left subclavian artery.

We describe the case of a 10-year-old boy with coarctation of the aorta complicated by innominate artery stenosis and agenesis of left common carotid artery and left subclavian artery. The patient was treated with an interposition graft between the ascending and descending aorta. The right subclavian was revascularized with another graft from the interposition graft to the distal right subclavian. This is a rare case of the combination of coarctation of the aorta and other vascular malformations.