RESUMEN
Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. COVID-19 patients with cardiovascular disorder (CVD) develop a more severe disease course with a significantly higher mortality rate than non-CVD patients. A common denominator of CVD is the dysfunction of endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in COVID-19 patients suffering from CVD are caused by SARS-CoV-2 infection of ECs through the angiotensin-converting enzyme 2 (ACE2) receptor and the cellular transmembrane protease serine 2 (TMPRSS2) and the consequent dysfunction of the infected vascular cells. Meanwhile, other factors associated with SARS-CoV-2 entry into the host cells have been described, including disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), the C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss the current data about the putative entry of SARS-CoV-2 into endothelial and smooth muscle cells. Furthermore, we highlight the potential role of long non-coding RNAs (lncRNAs) affecting vascular permeability in CVD, a process that might exacerbate disease in COVID-19 patients.
Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , ARN Largo no Codificante , Humanos , SARS-CoV-2 , ARN Largo no Codificante/genética , Células Endoteliales/metabolismo , Peptidil-Dipeptidasa A/metabolismoRESUMEN
Acute gouty arthritis (AGA) is characterized by the accumulation of proinflammatory cytokines, which are immunological responses to monosodium urate (MSU) crystals. It has been demonstrated that long noncoding RNA (lncRNA)MM2P is a novel regulator of M2 polarization of macrophages. The aim of the present study was to investigate whether lncRNAMM2P regulates the MSUinduced inflammatory process. In cell models of RAW 264.7 and THP1derived macrophages, decreased expression of lncRNAMM2P was observed in lipopolysaccharide and MSUtreated macrophages, which was accompanied with obvious inflammatory responses. Using small interfering RNA to knockdown lncRNAMM2P led to the upregulation of MSUmediated inflammatory responses, both in RAW 264.7 and THP1derived macrophages. In conclusion, lncRNAMM2P could be an important regulator of MSUinduced inflammation, and therefore could be involved in the development of AGA.
Asunto(s)
Artritis Gotosa/genética , Citocinas/genética , Lipopolisacáridos/efectos adversos , ARN Largo no Codificante/genética , Ácido Úrico/efectos adversos , Animales , Artritis Gotosa/inmunología , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Modelos Biológicos , Células RAW 264.7 , Células THP-1RESUMEN
The present prospective study was conducted to investigate the independent risk and predictive value of plasma long noncoding RNA metastasisassociated lung adenocarcinoma transcript 1 (MALAT1) as a biomarker for the diagnosis, severity and prognosis of sepsis. A total of 120 patients with sepsis and 60 healthy controls (HCs) were recruited. The expression levels of plasma MALAT1 were detected by quantitative PCR. The results demonstrated that the plasma levels of MALAT1 were significantly increased in patients with sepsis compared with HCs (P<0.001), in patients with septic shock compared with in patients without septic shock (P<0.001), and in nonsurvivors compared with in survivors (P<0.001). MALAT1 plasma levels exhibited weak positive correlation with serum procalcitonin levels (r=0.253; P=0.005), arterial lactate levels (r=0.488; P<0.001), sepsisrelated organ failure assessment scores (r=0.566; P<0.001), and acute physiology and chronic health evaluation II scores (r=0.517; P<0.001) in patients with sepsis. Multivariate logistic regression analysis revealed that high MALAT1 expression was an independent risk factor for sepsis (P<0.001), septic shock (P=0.030) and poor prognosis (P=0.015). In addition, the receiver operating characteristic curve exhibited a significant predictive value for MALAT1 in distinguishing patients with sepsis from HCs with an area under the curve (AUC) of 0.910, patients with septic shock from patients without shock with an AUC of 0.836, and nonsurvivors from survivors with an AUC of 0.886. In conclusion, plasma MALAT1 may serve as a biomarker for the diagnosis, severity and prognosis of sepsis.
Asunto(s)
ARN Largo no Codificante/sangre , Índice de Severidad de la Enfermedad , Choque Séptico , Adulto , Biomarcadores/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/sangre , Choque Séptico/sangre , Choque Séptico/diagnóstico , Choque Séptico/mortalidad , Tasa de SupervivenciaRESUMEN
Long noncoding RNAs (lncRNAs) have been classically defined as regulatory RNA members >200 nucleotides in length, without detectable openreading frames to encode proteins. Previous studies have demonstrated that lncRNAs serve critical roles in multiple cancer types. Colon cancerassociated transcript 1 (CCAT1), a novel cancerassociated lncRNA, is significantly overexpressed in a number of malignancies. Functionally, as an oncogenic lncRNA, CCAT1 is involved in proliferation, migration, cell cycle progression, apoptosis, chemoresistance and other biological processes of cancer cells through complex regulation mechanisms in the cytoplasm or nucleus. In clinical applications, CCAT1 is additionally positively associated with histological differentiation, tumour node metastasis stage, vascular invasion, overall survival and recurrencefree survival, which demonstrates its important role as a diagnostic and prognostic marker in cancer. The present review summarises the current research progress of the oncogenic potential and clinical uses of CCAT1 in various human cancer types.
Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/patología , ARN Largo no Codificante/genética , Apoptosis/genética , Carcinogénesis/genética , Diferenciación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Oncogenes/genética , PronósticoRESUMEN
The interactions of microRNAs (miRNAs), transcription factors (TFs) and their common target long noncoding RNAs (lncRNAs) can lead to the production of TFmiRNAlncRNA (TML) network motifs. These motifs are functional regulators that perform a wide range of biological processes, such as carcinogenesis. However, TML network motifs have not been systematically identified, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, a computational integration approach was performed using multiple sources in order to construct a global TML network for LUAD and LUSC. The analysis revealed several dysregulated TML network motifs, which were common between the two lung cancer subtypes or specific to a single cancer subtype. In addition, functional analysis further indicated that the TML network motifs may potentially serve as putative biomarkers in LUAD and LUSC. The associations between drug treatments and dysregulated TML network motifs were also examined. Collectively, the present study elucidated the roles of TML network motifs in LUAD and LUSC, which may be beneficial for understanding the pathogenesis of lung cancer and its potential treatment.