RESUMEN
Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.
RESUMEN
Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.
Asunto(s)
Enfermedades Cardiovasculares , ARN Largo no Codificante , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/fisiopatología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Predisposición Genética a la EnfermedadRESUMEN
Introduction: Cardiometabolic diseases are a global public health problem, with significant increases in their prevalence. Different epigenetic factors involved in the progression of metabolic alterations have been described, such as long non-coding RNAs (lncRNAs). H19 is a multifunctional lncRNA expressed from the maternal allele, with low expression after birth, except in the skeletal muscle and heart. Recent studies have linked its dysregulation to alterations in cell metabolism.Areas covered: H19 plays a role in the pathogenesis of coronary artery disease, nonalcoholic fatty liver disease, hepatic and renal fibrosis, insulin resistance, type 2 diabetes, and inflammation. H19 acts mainly as a competitive endogenous RNA of molecules involved in pathways that regulate cell metabolism. In this review, we analyzed the dysregulation of H19 in cardiometabolic diseases and its relationship with molecular alterations in different signaling pathways.Expert opinion: The association of H19 with the development of cardiometabolic diseases, indicates that H19 could be a therapeutic target and prognostic biomarker for these diseases. Controversies have been reported regarding the expression of H19 in some metabolic diseases, therefore, it is necessary to continue research to clarify its pathogenic effect in different organs.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , ARN Largo no Codificante , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/genética , Genes Supresores de Tumor , Humanos , Hígado/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
OBJECTIVES: To investigate the predictive value of long non-coding RNA (lncRNA) H19 and the ten-eleven translocation enzyme 1 (TET1) transcriptional expression in postoperative recurrence of uterine fibroids (UFs). METHODS: Seventy-five patients with UF, who underwent surgical treatment, were enrolled in the treatment group, and 60 healthy individuals were enrolled in the control group. The relative expression levels of lncRNA H19 and TET1 mRNA in the serum and UF tissues were analyzed. The patients were further divided into a better curative (BC) group and a poor efficacy (PE) group to analyze the predictive value of lncRNA H19 and TET1 and the independent risk factors affecting the recurrence of UF. RESULTS: Compared with the control group, lncRNA H19 expression levels were significantly higher, while TET1 expression levels were significantly lower in the treatment group (p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) values of the two indicators for diagnostic importance were found to be 0.872 and 0.826, respectively. Compared with the PE group, lncRNA H19 expression levels were significantly lower, while TET1 expression levels were significantly higher in the BC group (p<0.001). The AUC values of the two indicators for their predictive efficacy were 0.788 and 0.812, respectively. Logistic regression analysis showed that age, menarche age, maximum diameter of UFs, number of UFs, lncRNA H19 levels, and TET1 levels were independent risk factors affecting UF recurrence. The AUC values of lncRNA H19 and TET1 for their predictive value for postoperative recurrence were 0.814 and 0.765, respectively. CONCLUSIONS: The lncRNA H19 and TET1 have high diagnostic and predictive efficacy for determining the postoperative recurrence of UFs.
Asunto(s)
Humanos , Femenino , ARN Largo no Codificante/genética , Leiomioma , ARN Mensajero , Curva ROC , Proteínas Proto-Oncogénicas , Oxigenasas de Función Mixta , Recurrencia Local de NeoplasiaRESUMEN
The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.
Asunto(s)
Humanos , Animales , Femenino , Conejos , Endometriosis/genética , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , Proliferación Celular/genética , Endometrio , Ratones DesnudosRESUMEN
Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities.