RESUMO
Long noncoding RNAs (lncRNAs) serve a crucial role in gastric cancer (GC) progression. However, the molecular mechanism underlying lncRNA JPX transcript, XIST activator (JPX) in the tumorigenesis of GC is not completely understood. Reverse transcriptionquantitative PCR (RTqPCR) and western blotting were performed to detect gene expression. A luciferase reporter gene assay was conducted to determine the relationship between microRNA (miR)197 and JPX or CXC motif chemokine receptor 6 (CXCR6). Cell viability, migration and invasion were determined by performing MTT, wound healing and Transwell assays, respectively. The Cancer Genome Atlas database and the RTqPCR results indicated that JPX expression was upregulated and miR197 expression was downregulated in patients with GC and in GC cells. Moreover, high JPX expression and low miR197 expression in patients with GC indicated poor prognosis. miR197 expression was directly inhibited by JPX. Compared with the short hairpin RNA (sh) negative control (NC) group, NCIN87 and MKN45 cells in the shJPX group displayed decreased cell viability and invasion, as well as a wider scratch width. NCIN87 and MKN45 cells in the shJPX + miR197 inhibitor group had increased viability and invasion, but a narrower scratch width compared with the shJPX group. It was also identified that miR197 directly inhibited CXCR6 expression. miR197 inhibited Beclin1 protein expression and promoted p62 protein expression. Compared with the NC group, NCIN87 and MKN45 cells in the miR197 mimic group had decreased cell viability and invasion, and a wider scratch width. Enhanced cell viability and invasion, and a narrower scratch width was also observed in the miR197 mimic + CXCR6 and miR197 mimic + Beclin1 groups, compared with the miR197 mimic group. Collectively, the results indicated that lncRNA JPX promoted GC progression by regulating CXCR6 and autophagy via inhibiting miR197. Furthermore, JPX knockdown regulated GC cell phenotype by promoting miR197.
Assuntos
Autofagia/genética , MicroRNAs/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptores CXCR6/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , Receptores CXCR6/antagonistas & inibidores , Regulação para CimaRESUMO
In-stent restenosis (ISR) is the most common complication associated with percutaneous coronary intervention (PCI). Although some studies have reported an association between lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and ISR, not enough clinical validation data are available to support this link. Here, we report our cross-sectional study aimed at exploring the feasibility of LOX-1 as a biomarker for the prognostic diagnosis of patients undergoing PCI.Three groups were included: ISR group, including 99 patients with ISR diagnosed with coronary arteriography (CAG) after PCI; lesion group, comprising 87 patients with coronary artery stenosis (<50%) diagnosed with CAG after PCI; and control group, consisting of 96 volunteers with no coronary artery disease. The levels of LOX-1 were measured in each patient by using an enzyme-linked immunosorbent assay, and their general information as well as laboratory parameters were recorded and followed up during a period of 2 years.LOX-1 levels gradually increased after PCI along with the progression of the lesion in the 3 groups. The levels of LOX-1 were significantly higher in the ISR group than in the other 2 groups (Pâ<â.001). LOX-1 levels were correlated with the levels of uric acid (UA) (râ=â0.289, Pâ=â.007), creatinine (CREA) (râ=â.316, Pâ=â.003), and high-density lipoprotein cholesterol (HDL-C) (râ=â-0.271, Pâ=â.012), whereas no statistically significant correlation was detected with the Gensini score (râ=â0.157, Pâ=â.141). The sensitivity and specificity of LOX-1 were 81.5% and 55.7%, respectively, with the most optimal threshold (5.04âµg/L). The area under curve (AUC) of the receiver operator characteristic (ROC) curve of LOX-1 was 0.720, and LOX-1 had the highest AUC compared with CREA, UA, and HDL-C, both individually and in combination.A high level of LOX-1 in the early period after PCI has a certain predictive power and diagnostic value for ISR. However, the level of LOX-1 is not related to the Gensini score of coronary artery after PCI, and CREA and UA, which are weakly related to LOX-1, have no obvious synergy in the diagnosis of ISR with LOX-1.
Assuntos
Reestenose Coronária/sangue , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Receptores Depuradores Classe E/sangue , Fatores Etários , Idoso , Índice de Massa Corporal , Comorbidade , Constrição Patológica , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores SexuaisRESUMO
Rapid and accurate differential diagnosis of acute myocardial infarction (AMI) is crucial for timely interventions and the improvement of prognosis. However, this is difficult to achieve using current methods. Therefore, the present study aimed to evaluate the suitability of circulating microRNAs (miRNAs) as AMI biomarkers in patients with acute coronary syndrome (ACS). miRNA profiling in plasma samples from patients with AMI (n=3) and healthy controls (n=3) was performed using microarrays. Results were then validated in five patients and five healthy controls. miRNA-125b-5p and miR-30d-5p expression levels were quantified in plasma samples from 230 patients with ACS and 79 healthy controls using reverse transcription-quantitative polymerase chain reaction. Routine diagnostic parameters were assessed, including creatinine kinase MB, cardiac troponin I (cTnI) and myoglobin. A total of 33 miRNAs were differentially expressed in patients with AMI and healthy controls. Following validation based on the previously established roles for these miRNAs, six miRNAs were validated. miR125b5p and miR30d5p were selected for further investigation. Expression levels of miR125b5p and miR30d5p in plasma were higher in patients with ACS compared with the healthy controls (P<0.001). Receiver operating characteristic curve analysis revealed that the area under the curve of miR30d5p was higher than that of cTnI (0.915 and 0.899). miR125b5p (sensitivity, 0.808; specificity, 0.845) and miR30d5p (sensitivity, 0.855; specificity, 0.810) were suitable diagnostic predictors of AMI. Kaplan-Meier survival analysis indicated that miR-125b-5p levels were associated with 6 month cardiovascular events in patients with AMI, but not miR30d5p. miR-125b-5p and miR-30d-5p presented a diagnostic value for early diagnosis of AMI, and miR30d5p may have a higher diagnostic value than cTnI.
Assuntos
MicroRNAs/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Análise por Conglomerados , Comorbidade , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
The typical breakpoint cluster region/Abelson (BCR-ABL) fusion gene, which is located in the Philadelphia chromosome, in association with a complex translocation event is only observed in 2-10% of patients with chronic myelogenous leukemia (CML). CML is diagnosed based on the presence of splenomegaly, increased peripheral white blood cells and the expression of BCR-ABL. The present study reports the case of a patient with CML that possessed complex aberrations involving 5 chromosome translocations, which consisted of t(1;6)(p36.1;q25) and t(9;22;11)(q34;q11.2;q11). After 2 months of follow-up, the patient is in remission following treatment with imatinib (400 mg/day) and hydroxyurea (3,000 mg/day). The hematological parameters of the patient were significantly improved and the white blood cell count returned to normal (from 361.00×109 cells/l to 6.83×109cells/l; normal range, 3.50-9.50×109 cells/l). The results of the ultrasonic examination revealed that the presence of splenomegaly had disappeared, indicating that the treatment strategy was effective. According to the outcome of the treatment, hydroxyurea in combination with imatinib is recommended for use in similar cases of CML.