RESUMEN
Nonalcoholic fatty liver disease (NAFLD) poses serious threats to humans. Several studies have studied the biomarkers associated with NAFLD; however, the results vary because of the differences in the sequencing platform, sample selection, and filter conditions. This study aimed to explore the key microRNAs (miRNAs) of NAFLD by a systematic bioinformatics analysis. A total of 10 qualified NAFLD miRNA data sets were selected through a literature review. Signature miRNAs were identified by overlap comparison. The target genes of miRNAs were predicted by TargetScan software and functional enrichment, and transcription factor (TF) binding analysis of target genes was carried out by the database for annotation, visualization, and integrated discovery and Tfacts database, respectively. A total of three upregulated miRNAs and five downregulated miRNAs were identified in the NAFLD tissue. The target genes of upregulated miRNAs mainly enriched in the RNA polymerase II promoter transcriptional regulation, chromatin remodeling process, and O-glycan synthesis, circadian rhythm, and endocytosis; the target genes of downregulated miRNAs mainly enriched in the transcriptional regulation of DNA as a template, negative regulation process of protein phosphorylation, and Fc epsilon RI signaling pathways, Ras signaling pathways and the interaction between cytokines and cytokines. Besides, 136 interactions were formed between 62 TFs and 45 target genes of upregulated miRNA, whereas 157 interactions were formed between 72 TFs and 45 target genes of downregulated miRNA. Both contained 102 TFs, and 32 TFs were present in both target genes. To summarize, we identified an eight-miRNA set as a signature for NAFLD, which will benefit the clinical treatment of NAFLD.
Asunto(s)
Regulación de la Expresión Génica/genética , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , ARN Mensajero/genética , Biomarcadores/metabolismo , Biología Computacional/métodos , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/genética , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Mensajero/metabolismoRESUMEN
Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Quimiocinas CC/genética , Lectinas Tipo C/genética , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , Biomarcadores de Tumor/biosíntesis , Carcinoma Hepatocelular/patología , Quimiocinas CC/biosíntesis , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Lectinas Tipo C/biosíntesis , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana/biosíntesis , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Recent studies have indicated that long non-coding RNAs (lncRNAs) play important regulatory roles in tumor development and progression. However, the contribution of small nucleolar RNA host gene 20 (SNHG20) to gastric cancer development remains largely unknown. The aim of the study is to investigate the functional significance of SNHG20 involved in gastric cancer (GC) progression. In the study, our results demonstrated that the expression levels of SNHG20 were remarkably up-regulated in GC cells. Functionally, SNHG20 promoted the GC MKN45 and BGC-823 cells proliferation and invasion. Furthermore, knockdown of SNHG20 significantly inhibited the epithelial-mesenchymal transition (EMT) in MKN45 and BGC-823 cells, whereas, the overexpression of SNHG20 had the promoting effects. Moreover, we found that overexpression of SNHG20 in MKN45 and BGC-823 cells significantly inhibited the expression of E-cadherin and p21 via binding to EZH2 and regulated the GSK-3ß/ß-catenin signaling pathway. Thus, the results showed that SNHG20 acted as an oncogene in GC and targeting SNHG20 may serve as a therapeutic target for GC.