RESUMEN
Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence; piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial-mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-ß (TGF-ß) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/ß-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE.
Asunto(s)
Exosomas , Lupus Eritematoso Sistémico , Nefritis Lúpica , MicroARNs , ARN Largo no Codificante , Humanos , Nefritis Lúpica/diagnóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Riñón/metabolismo , Exosomas/genética , Exosomas/metabolismo , ARN de Interacción con PiwiRESUMEN
To investigate the prospective roles and the clinicopathological application of microRNA-21-5p (miR-21-5p) in hepatocellular carcinoma (HCC), the present review is based on 24 studies and bioinformatics investigation. Firstly, HCC-associated miR-21-5p data were aggregated from literature databases and two public genomic data repositories, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Potential target genes of miR-21-5p in HCC were identified using TCGA and GEO, Natural Language Processing and 14 online software packages. The oncogenic roles of these target genes was probed for understanding using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Hub genes were further investigated by protein-protein interaction network (PPI) analysis. Comprehensive meta-analysis, including 10 microarrays from GEO datasets, 13 literature studies and TCGA-based RNA sequencing data, indicated a reliable diagnostic capacity of miR-21-5p [area under the curve (AUC), 0.887; sensitivity, 0.78% and specificity, 0.79%]. The healthy control group (AUC, 0.926; sensitivity, 0.87% and specificity, 0.82%) demonstrated high diagnostic capacity of miR-21-5p compared with the chronic hepatitis B infection group (AUC, 0.904; sensitivity, 0.75% and specificity, 0.84%). A total of 10 significant enrichment pathways were indicated by KEGG analysis, with cytokine-cytokine receptor interaction exhibiting the highest score. A total of 5 genes, hepatocyte growth factor, forkhead box O1 (FOXO1), thrombospondin 1, estrogen receptor 1 (ESR1) and C-X-C motif chemokine ligand 12 were selected from 39 overlapping genes, according to the PPI network. Target genes were assembled in GO terms associated with 'response to chemical stimulus', 'cell surface' and 'growth factor binding'. In particular, low expression of FOXO1 and ESR1 was associated with miR-21-5p expression. In conclusion, upregulated expression of miR-21-5p may be a functional regulator of the metabolism or apoptosis in HCC and a novel tumor marker for the early diagnosis of HCC.
RESUMEN
MicroRNAs (miRNAs) are involved in the pathogenesis of diverse types of malignancies, including hepatocellular carcinoma (HCC). However, miR-365 has rarely been reported in HCC. The purpose of the current study was to identify the clinical relevance of miR-365 in HCC and examine the potential downstream signaling effectors.Using real-time RT-qPCR, we confirmed that miR-365 expression was markedly decreased in HCC tissues (3.5138 ± 2.2527) compared to that in paraneoplastic liver tissues (6.5950 ± 4.1230, P<0.001). Receiver operating characteristic curves to assess the diagnostic value of miR-365 in HCC demonstrated that the area under the curve was 0.757. Furthermore, down-regulation of miR-365 was remarkably correlated to the number of tumor nodes, status of metastasis, clinical TNM stage, portal vein tumor embolus and vaso-invasion. In addition to the clinical value of miR-365, a total of 238 downstream direct targets selected by online predictive algorithms and key genes generated from natural language processing and the Cancer Genome Atlas (TCGA) were pooled for bioinformatics analysis. These potential targets were mainly enriched in the Ras Pathway using PANTHER analysis and the 'Pathways in Cancer' using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In conclusion, down-regulated miR-365 may contribute to the progression and metastasis of HCC via targeting multiple signaling pathways, and miR-365 may act as a novel biomarker for HCC.