miR-143 Interferes with ERK5 Signaling, and Abrogates Prostate Cancer Progression in Mice

Abstract Background: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo. Results: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer. Conclusions: miR-143 is as a new target for prostate cancer treatment.

A highly expressed miR-101 isomiR is a functional silencing small RNA

Background MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5" or 3" of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5"-trimming variant (5"-isomiR-101). Results The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5"-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5"- isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5"-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5"-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5"-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5"-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5"-isomiR-101. Conclusions These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

El examen MIR y su contenido en anatomía humana, bioestadística y epidemiología: evolución y accesibilidad para el opositor/a

Fundamentos: El examen MIR constituye actualmente el único medio de selección de candidatos para la formación de médicos especialistas en España. Consta de 260 preguntas (10 de ellas son de reserva) de las distintas asignaturas de la licenciatura de medicina. El presente estudio pretende describir la evolución de los contenidos en anatomía humana, bioestadístíca y epidemiología de las distintas convocatorias MIR realizadas desde 1982. Métodos: Se analizaron todos los exámenes MIR generales desde 1982 hasta 1996, incluidas las convocatorias específicas de medicina familiar y comunitaria desde 1995 a 1997. En cada examen, se identificaron los contenidos de todas las preguntas relacionadas con anatomía humana, bioestadistica y epidemiología, según una clasificación en categorías temáticas adaptada de los programas docentes de cada asignatura. El tratamiento estadístico consistió en el análisis descriptivo (tabulación y representación gráfica) de las categorías temáticas y de su accesibilidad para un hipotético opositor/a con unos determinados conocimientos. Resultados: El número de preguntas de cada una de dichas asignaturas no superó en ninguna convocatoria general el 4% del total de preguntas. Las categorías temáticas con mayor frecuencia de aparición fueron, en anatomía humana, extremidad superior e inferior; en bioestadística, probabilidad/pruebas diagnósticas, y epidemiología descriptiva para el caso de epidemiología. Un hipotético opositor/a que no se preparó ningún tema de anatomía humana, bioestadística o epidemiología tan sólo tuvo acceso, respectivamente, a 1, 6 o 3 de las 15 convocatorias generales MIR revisadas. Conclusiones: En el examen MIR, la presencia de contenidos de anatomía humana tiende a disminuir, mientras que los de bioestadística y epidemiología cobran mayor importancia. Un/a opositor/a que domine los conocimientos adquiridos durante su licenciatura tiene acceso temático a la totalidad de preguntas de dichas asignaturas.

Cent anys del professor Joaquim Carreras i Artau

Homenatge a la figura, més aviat desconeguda, del filòsof gironí Joaquim Carreras i Artau, autor d’un treball de qualitat, silenciós i constant, útil, intel·lectual i pedagògic, segons l’autor de l’article