RESUMEN
BACKGROUND: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate. OBJECTIVES: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients. METHODS: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells. RESULTS: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients' 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability. CONCLUSION: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , MicroARNs , Humanos , Lipopolisacáridos/toxicidad , Células A549 , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Biomarcadores , Inflamación/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismoRESUMEN
BACKGROUND: Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis. OBJECTIVE: In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC. METHODS: Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting. RESULTS: UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p. CONCLUSION: These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.
Asunto(s)
MicroARNs , Neoplasias Ováricas , ARN Largo no Codificante , Femenino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Ováricas/genética , ARN Mensajero , Proteínas Serina-Treonina QuinasasRESUMEN
MicroRNAs (miRNAs/miRs) have important roles in inflammation and infections, which are common manifestations of acute respiratory distress syndrome (ARDS). The present study aimed to assess whether serum miRNAs are potential diagnostic biomarkers for human ARDS. For this, two sets of serum samples from healthy individuals and patients with ARDS were analysed by high-throughput sequencing to identify differentially expressed genes in ARDS. A total of 679 valid sequences were identified as differentially expressed (P<0.05). Of these, five differentially expressed miRNAs were subjected to reverse transcription-quantitative PCR validation. Finally, two miRNAs (miR-584 and miR-146a) were successfully verified. These two miRNAs were significantly downregulated in the serum of patients with ARDS. Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that their target transcripts were implicated in a broad range of biological processes and various metabolic pathways, including involvement in the regulation of various inflammatory factors. The present study provided a framework for understanding the molecular mechanisms of ARDS and suggested that miR-584 and miR-146a are associated with ARDS and may be potential therapeutic targets.