RESUMEN
We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.
Asunto(s)
Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Anciano , Análisis por Conglomerados , Metilación de ADN , Humanos , MicroARNs/genética , Persona de Mediana Edad , Músculo Liso/patología , ARN Largo no Codificante/genética , Análisis de Supervivencia , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
Hydrogen sulfide (H2S) is an air pollutant, has toxic effects on respiratory tract. However, the underlying mechanisms of H2S induced respiratory toxicity and the roles of long non-coding RNAs (lncRNA) and microRNA (miRNA) in this process remain poorly understood. To clear this, we investigated the change of tracheal tissue ultrastructure and the expression profiles of lncRNAs and miRNAs of chicken trachea exposed to H2S for 42â¯days. Results showed that H2S exposure triggered apoptosis, necroptosis, and differential expression of 16 lncRNAs and 18 miRNAs in broiler tracheas. The results of LMH cells stimulated by NaHS in vitro also showed the occurrence of apoptosis and necroptosis. LncRNA3037 is down-regulated and miR-15a is up-regulated in tracheal tissue and LMH cells under H2S exposure. Bioinformatics analysis and dual luciferase reporter system showed lncRNA3037 bound directly to miR-15a and negatively regulates each other. A20 and BCL2 are the target genes of miR-15a and negatively regulated by it. Overexpression of miR-15a caused apoptosis and necroptosis and its inhibition partially reversed apoptosis and necroptosis of LMH cells caused by NaHS stimulation and lncRNA3037 knockdown. Taken together, we concluded that H2S exposure mediates apoptosis and necroptosis through lncRNA3037/miR-15/A20-BCL2. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.