RESUMO
Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen α-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit α (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.
RESUMO
miR-193a-3p is a tumor-related miRNA playing an essential role in tumorigenesis and progression of non-small cell lung cancer (NSCLC). The objective of the present study was to investigate the relationship between miR-193a-3p expression and clinical value and to further explore the potential signaling of miR-193a-3p in the carcinogenesis of NSCLC. RNA-sequencing and microarray data were collected from the databases GEO, ArrayExpress and The Cancer Genome Atlas (TCGA). Furthermore, in silico assessments were performed to analyze the prospective pathways and networks of the target genes of miR-193a-3p. In total, 453 cases of NSCLC patients and 476 normal controls were included in blood samples, while 920 cases of NSCLC patients and 406 normal controls were included in tissue samples. The pooled positive likelihood ratio, the pooled negative likelihood ratio and the pooled diagnostic odds ratio were calculated to reflect the diagnostic value of miR-193a-3p in blood and tissue samples. Moreover, the areas under the curve of the summary receiver operating characteristic curve of blood and tissue were 0.64 and 0.79, respectively. In addition, we found a lower level of miR-193a in NSCLC tissues than in non-cancerous controls based on TCGA. A gene ontology (GO) enrichment analysis demonstrated that miR-193a-3p could be related to key signaling pathways in NSCLC. Also, several vital pathways were illustrated by KEGG. Lower expression of miR-193a-3p in tissue samples of NSCLC may be associated with tumorigenesis and be a predictor of deterioration of NSCLC patients, and pathway analysis revealed crucial signaling pathways correlated with the incidence and progress of NSCLC.
