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Human aortic vascular smooth muscle cells (HA-VSMCs) play vital roles in the pathogenesis of vascular diseases, including Atherosclerosis (AS). Circular RNAs (circRNAs) have been reported to regulate the biological functions of HA-VSMCs. Therefore, this study aimed to explore the role and mechanism of hsa_circRNA_102353 (circ_0007765) in platelet-derived growth factor-BB (PDGF-BB)-induced HA-VSMCs. Circ_0007765, microRNA-654-3p (miR-654-3p), and Fibroblast Growth Factor Receptor Substrate 2 (FRS2) expression were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, invasion, and migration were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and wound healing assays. CyclinD1, MMP2, and FRS2 protein levels were assessed using a Western blot assay. Binding between miR-654-3p and circ_0007765 or FRS2 was predicted by Circinteractome or TargetScan, and verified using dual-luciferase reporter and RNA pull-down assays. PDGF-BB induced HA-VSMC proliferation, invasion, and migration. Circ_0007765 and FRS2 expression levels were increased in PDGF-BB-treated HA-VSMCs, and the miR-654-3p level was reduced. Moreover, circ_0007765 absence hindered PDGF-BB-induced HA-VSMC proliferation, invasion, and migration in vitro. At the molecular level, circ_0007765 increased FRS2 expression by acting as a sponge for miR-654-3p. Our findings revealed that circ_0007765 boosted PDGF-BB-induced HA-VSMC proliferation and migration through elevating FRS2 expression via adsorbing miR-654-3p, providing a feasible therapeutic strategy for AS.
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Introduction: Although heart failure (HF) has been linked to bisphenol A (BPA), few studies have investigated the cut-off values for the effects of urinary BPA levels on heart failure risk. The association between urinary BPA levels and HF prognosis has not been investigated. Methods: This study included 11,849 adults over 20 years old using information from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2003 to 2016. The relationship between urinary BPA levels and the risk of HF was determined via a multivariable logistic regression model, and restricted cubic spline (RCS) methods were used to determine the cut-off for the effect of BPA levels on HF risk. Based on the available NT-proBNP concentration data from the NHANES (2003-2004), multivariable linear regression was applied to determine the linear association between the NT-proBNP concentration and urinary BPA concentration. Results: The results revealed a positive correlation between a urinary BPA concentration in the fourth quartile and the occurrence of heart failure [OR 1.49, 95% CI (1.09, 2.04), p = 0.012]. A one-unit increase (1â ng/mg creatinine) in the ln-transformed BPA concentration was linked to a 15% increase in the incidence of HF [OR 1.15, 95% CI (1.03, 1.29), p = 0.014]. The cut-off urinary BPA concentration for HF risk was 1.51â ng/mg creatinine. There was a positive correlation between urinary BPA and NT-proBNP concentrations [ß = 0.093, 95% CI (0.014, 0.171), p = 0.02] in males, but there was no linear association [ß = 0.040, 95% CI (-0.033, 0.113), p = 0.283] in females. Discussion: Increased urinary BPA levels are linked to an increased risk of heart failure and poor prognosis. There is a significant increase in the risk of heart failure if the urinary concentration of BPA exceeds 1.51â ng/mg creatinine.
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Circular RNA (circRNAs) has been confirmed to participate in atherosclerosis (AS) progression. However, the role and mechanism of hsa_circ_0032389 in AS process still need to be further revealed. This study evaluates the role and mechanism of hsa_circ_0032389 in AS process. Platelet-derived growth factor-BB (PDGF-BB) was used to induce human aortic vascular smooth muscle cells (HA-VSMCs). The expression levels of hsa_circ_0032389, microRNA (miR)-513a-5p, and fibroblast growth factor receptor substrate 2 (FRS2) were examined by quantitative real-time PCR. Cell proliferation and migration were analyzed using cell counting kit 8 assay, flow cytometry, EdU assay, transwell assay, and wound healing assay. Protein expression was assessed using western blot analysis. Dual-luciferase reporter and RIP assays were used to confirm RNA interaction. Hsa_circ_0032389 was overexpressed in PDGF-BB-induced HA-VSMCs, and its downregulation inhibited HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate under PDGF-BB treatment. The luciferase activity of hsa_circ_0032389wt could be reduced by miR-513a-5p mimic, and both hsa_circ_0032389 and miR-513a-5p were enriched in anti-Ago2, confirming that miR-513a-5p could be sponged by hsa_circ_0032389. MiR-513a-5p inhibitor reversed the effect of hsa_circ_0032389 knockdown on PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate. Moreover, the luciferase activity of FRS2wt was reduced by miR-513a-5p mimic, and both FRS2 and miR-513a-5p were enriched in anti-Ago2, verifying that FRS2 was targeted by miR-513a-5p. MiR-513a-5p suppressed PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate by targeting FRS2. Our results indicated that hsa_circ_0032389 enhanced PDGF-BB-induced HA-VSMC proliferation and migration via regulating miR-513a-5p/FRS2 axis.
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Aterosclerosis , MicroARNs , Humanos , Becaplermina/farmacología , Músculo Liso Vascular , MicroARNs/genética , Proliferación Celular , Luciferasas , Movimiento CelularRESUMEN
Background: Lymph node metastasis is an important route of lung cancer metastasis and can significantly affect the survival of lung cancer. Methods: All the analysis was conducted out in the R software. Expression profile and clinical information of lung adenocarcinoma (LUAD) patients were downloaded from The Cancer Genome Atlas database. Results: In our study, we firstly identified the characteristic genes of lymph node metastasis in LUAD through two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression, and SVM-RFE algorithms. Ten characteristic genes were finally identified, including CRHR2, ITIH1, PRSS48, MAS1L, CYP4Z1, LMO1, TCP10L2, KRT78, IGFBP1, and PITX3. Next, we performed univariate Cox regression, LASSO regression, and multivariate Cox regression sequentially to construct a prognosis model based on MAS1L, TCP10L2, and CRHR2, which had a good prognosis prediction efficiency in both training and validation cohorts. Univariate and multivariate analysis indicated that our model is a risk factor independent of other clinical features. Pathway enrichment analysis showed that in the high-risk patients, the pathway of MYC target, unfolded protein response, interferon alpha response, DNA repair, reactive oxygen species pathway, and glycolysis were significantly enriched. Among three model genes, MAS1L aroused our interest and therefore was selected for further analysis. KM survival curves showed that the patients with higher MAS1L might have better disease-free survival and progression-free survival. Further, pathway enrichment, genomic instability, immune infiltration, and drug sensitivity analysis were performed to in-deep explore the role of MAS1L in LUAD. Conclusions: Results showed that the signature based on MAS1L, TCP10L2, and CRHR2 is a useful tool to predict prognosis and lung cancer lymph node metastasis.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Metástasis Linfática/genética , Especies Reactivas de Oxígeno/metabolismo , Estimación de Kaplan-Meier , Regulación Neoplásica de la Expresión Génica , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/metabolismo , Aprendizaje Automático , Interferón-alfa/genética , Interferón-alfa/metabolismo , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismoRESUMEN
Activation and proliferation of cancer stem cells exert an important role in the invasion, metastasis, and recurrence of malignant tumors, including lung cancer. Therefore, exploring molecular targets related to self-renewal and mobility of lung cancer stem cells has important clinical significance. In our present study, we aimed to explore the effects of miR-138-5p on lung cancer stem-like cells and associated regulatory mechanism. In our present study, enhanced self-renewal capacity and elevated expression of cancer stem cells markers CD133, CD44, aldehyde dehydrogenase 1 of lung cancer stem-like cells derived from A549 cells were firstly verified. Then, obviously enhanced autophagy was found in lung cancer stem-like cells compared with parental cells A549. Besides, we found that enhanced autophagy induced by rapamycin promoted self-renewal and cell mobility of lung cancer stem-like cells and suppression of autophagy by 3-methyladenine exerted just opposite effects. In addition, miR-138-5p was found to be downregulated in lung cancer stem-like cells compared with that in parental cell A549. At the same time, overexpression of miR-138-5p by transfected with miR-138-5p mimic was found to effectively suppress self-renewal and invasion of lung cancer stem-like cells. Further study revealed that ATG7 was a target of miR-138-5p and overexpressed miR-138-5p suppressed ATG7-mediated autophagy. In addition, specific small interference RNA-ATG7 strengthened the inhibiting effect of miR-138-5p mimic on self-renewal and invasion of lung cancer stem-like cells. Taken together, we found that autophagy helped to maintain self-renewal and invasion ability of lung cancer stem-like cells and overexpressed miR-138-5p exerted anti-tumor effects by blocking the self-renewal and invasion of lung cancer stem-like cells through suppressing ATG7-mediated autophagy.
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Proteína 7 Relacionada con la Autofagia/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Células Madre Neoplásicas/patología , Células A549 , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Autofagia/efectos de los fármacos , Autofagia/fisiología , Autorrenovación de las Células/efectos de los fármacos , Autorrenovación de las Células/fisiología , Regulación hacia Abajo , Humanos , Neoplasias Pulmonares/genética , MicroARNs/administración & dosificación , MicroARNs/biosíntesis , MicroARNs/genética , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Sirolimus/farmacología , TransfecciónRESUMEN
OBJECTIVES: Our goal was to compare the short-term outcomes of Stanford type A aortic dissection (TAAD), during the coronavirus disease 2019 (COVID-19) pandemic with those during normal times and summarize our perioperative management experience of patients with TAAD in the context of COVID-19. METHODS: From 17 January 2020 to 8 March 2020, a total of 27 patients with TAAD were operated on in 8 cardiovascular surgery centres in Hubei Province (COVID-19 group). The data from 91 patients with TAAD from the same centres during the same period last year were extracted from the Hubei Cardiac Surgery Registration System (control group). A propensity score matched subgroup of 26 pairs (1:2) was identified. Perioperative data and short-term outcomes were assessed. RESULTS: Nine patients in the COVID-19 group were categorized as suspicious for the disease (9/27, 33.3%), and others were excluded (18/27, 66.7%). No one was laboratory confirmed preoperatively. The average waiting, cross-clamp and circulatory arrest times were longer in the COVID-19 group (22.9 ± 8.3 vs 9.7 ± 4.0 h, P < 0.001; 135 ± 36 vs 103 ± 45 min, P = 0.003; 24 ± 9 vs 17 ± 8 min, P < 0.001, respectively). The 30-day or in-hospital deaths were 3.8% in both groups (P = 1.0). The COVID-19 group was associated with longer ventilation and intensive care unit times (81 ± 71 vs 45 ± 19 h, P < 0.001; 7.4 ± 3.8 vs 4.5 ± 2.7 days; P < 0.001, respectively). There were no statistical differences between the 2 groups in the incidence of complications such as stroke, neurological deficit, acute kidney injury, pulmonary infection and reoperation. Serum antibody tests for those patients showed 7 out of 9 suspected cases were Immunoglobulin G positive. No cross-infection occurred in other patients or associated medical staff. CONCLUSIONS: With adequate preparation and appropriate protection, satisfactory early outcomes can be achieved after emergency operations for patients with TAAD during the COVID-19 pandemic.
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Disección Aórtica/cirugía , COVID-19/epidemiología , Pandemias , Puntaje de Propensión , SARS-CoV-2 , Procedimientos Quirúrgicos Vasculares/métodos , Disección Aórtica/epidemiología , China/epidemiología , Comorbilidad , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
Non-small-cell lung cancer (NSCLC) is the fundamental form of lung cancer and the leading cause of cancerrelated mortality in humans. Numerous studies have identified a role for microRNAs (miRs) in cell proliferation, invasion and metastasis in numerous types of cancer, including lung cancer. In the present study, the functional roles and molecular mechanisms of miR28 in NSCLC tumorigenesis were investigated. Reverse transcriptionquantitative PCR (RTqPCR) was used to measure miR28 expression levels in NSCLC tumor tissues and cell lines. A dualluciferase assay was performed to observe the direct interaction between miR28 and PTEN in A549 cells. Furthermore, the effect of miR28 on the mRNA and protein expression levels of PTEN was examined by RTqPCR and western blotting, respectively. A Cell Counting kit8 assay was performed to identify the relationship between the miR28/PTEN axis and tumor cell proliferation using cells infected with lentivirus (LV)antimiR28 or LVantimiR28 + short hairpin RNAPTEN. miR28 expression was upregulated in NSCLC tumor tissues and cell lines compared with the control groups. PTEN was identified as the downstream gene of miR28 in NSCLC and was negatively regulated by miR28. In addition, miR28 knockdown suppressed the proliferation of A549 and H292 cells. Cells infected with LVantimiR28 + short hairpin RNAPTEN promoted tumor cell proliferation in A549 and H292 cells compared with cells infected with LVantimiR28. Taken together, the present study suggested that miR28 might serve as the promoter in the development of NSCLC by targeting PTEN. Therefore, the miR28/PTEN axis may serve as a potential diagnostic and therapeutic target for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , MicroARNs/farmacología , Fosfohidrolasa PTEN/metabolismo , Células A549 , Adulto , Carcinogénesis/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , ARN Interferente Pequeño/metabolismoRESUMEN
An increasing number of microRNAs (miRNAs/miRs) are reported to have important roles in diabetes. Glucosestimulated insulin secretion and pancreatic ß cell proliferation are essential in the control of metabolic disorder, however, the underlying molecular mechanisms remain unclear. The present study investigated the function of miR152 in diabetes. The results of reverse transcriptionquantitative polymerase chain reaction demonstrated that miR152 levels in the blood were markedly reduced in patients with diabetes compared with nondiabetic controls. In addition, a high blood glucose concentration was significantly associated with reduced miR152 expression. Furthermore, overexpression of miR152 using miR152 mimics promoted the proliferation of INS1 and MIN6 cells, as determined by an MTT assay, in addition to insulin secretion, while knockdown of miR152 using an inhibitor led to the opposite effects. Phosphatidylinositol 3kinase (PI3K) signaling has been reported to inhibit insulin secretion, however, the regulation of PI3K in the pancreatic ß cell is poorly understood. The present study identified that PI3K catalytic subunit α (PI3Kα) was a direct target gene of miR152 using a luciferase reporter assay, and miR152 inhibited the expression of PI3Kα at the protein level, which was determined by western blotting. Therefore, the regulation of insulin secretion and pancreatic ß cell proliferation may occur via the miR152/PI3Kα axis. The overexpression of PI3Kα in INS1 and MIN6 cells partially reduced the effects of miR152 overexpression on insulin secretion. Consistently, PI3Kα levels were reduced in murine pancreatic islets following treatment with 20 mM glucose, and increased in blood samples from patients with diabetes compared with healthy individuals. In conclusion, the results of the present study demonstrate that miR152 may have an important role in pancreatic ß cell function, and established an association between miR152 and the PI3Kα axis. Therefore, targeting PI3Kα may be a potential therapeutic option for diabetes.
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Secreción de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Animales , Secuencia de Bases , Línea Celular , Proliferación Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Glucosa/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de SeñalRESUMEN
Recently, emerging evidence has suggested that long noncoding RNAs (lncRNAs) have crucial roles in cancer progression. Here, we demonstrated that the lncRNA MIR4435-2HG was highly expressed in lung cancer tissues and correlated with histological grades and lymph node metastasis. Phenotypic analysis indicated that MIR4435-2HG knockdown inhibited lung cancer cell proliferation and invasion in vitro and in vivo. Notably, MIR4435-2HG knockdown suppressed the EMT (epithelial-mesenchymal transition) process and cancer stem cell traits of lung cancer cells. Mechanistically, MIR4435-2HG knockdown decreased the transactivation of ß-catenin. MIR4435-2HG interacted with ß-catenin and thus prevented its degradation by the proteasome system. Our findings highlight the important roles and mechanisms of MIR4435-2HG in lung cancer progression. High expression of lncRNA MIR4435-2HG correlates with lung cancer progression MIR4435-2HG promotes lung cancer cells proliferation and invasion MIR4435-2HG knockdown suppresses the EMT process and cancer stem cell traits MIR4435-2HG knockdown inhibits the ß-catenin signalling.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , beta Catenina/metabolismo , Adulto , Anciano , Animales , Línea Celular Tumoral , Movimiento Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patologíaRESUMEN
The deregulation of miR-101 has been implicated in multiple cancer types including lung cancer, but the exact role, mechanisms and how silencing of miR-101 remain elusive. Here we confirmed miR-101 downregulation in lung cancer cell lines and patient tissues. Restored miR-101 expression remarkably sensitized lung cancer cells to chemotherapy and inhibited invasion. Mechanistically, we indicated that miR-101 inversely correlated with RUNX1 expression, and identified RUNX1 as a novel target of miR-101. RUNX1 impaired the effects of miR-101 on chemotherapeutic sensitization and invasion inhibition. Moreover, RUNX1 knockdown resulted into increase of miR-101 expression and elevation of luciferase activity driven by miR-101 promoter in lung cancer cells, suggesting RUNX1 negatively transcriptionally regulated miR-101 expression via physically binding to miR-101 promoter. These findings support that miR-101 downregulation accelerates the progression of lung cancer via RUNX1 dependent manner and suggest that miR-101/RUNX1 feedback axis may have therapeutic value in treating refractory lung cancer.
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We investigate the electronic transport properties of coupled quantum dots, controlled by local gates on carbon nanotubes. The inter-dot coupling can be tuned from weak to strong by changing gate voltages, and oscillates in short and long period with the distance between two gates. We introduce a one-dimensional scattering model to describe the mechanism of the electron transport through the carbon nanotube quantum dots. We show that pi and PI* channels contribute differently to the inter-dot coupling and the transport phase plays a key role in the oscillations of the coupling.
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The intrinsic transport properties of zigzag graphene nanoribbons (ZGNRs) are investigated using first-principles calculations. It is found that although all ZGNRs have similar metallic band structure, they show distinctly different transport behaviors under bias voltages, depending on whether they are mirror symmetric with respect to the midplane between two edges. Asymmetric ZGNRs behave as conventional conductors with linear current-voltage dependence, while symmetric ZGNRs exhibit unexpected very small currents with the presence of a conductance gap around the Fermi level. This difference is revealed to arise from different coupling between the conducting subbands around the Fermi level, which is dependent on the symmetry of the systems.