To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-kappaB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.
BackgroundMiR-101-3p can promote apoptosis and inhibit proliferation, invasion, and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not fully understood. Therefore, a comprehensive analysis of the target genes, pathways, and networks of miR-101-3p in BC is necessary.Material/MethodsThe miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA) were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected MCF-7 cells and scramble control cells was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO) and pathway and network analyses were constructed for the DEGs and predicted genes.ResultsIn the TCGA data, a low level of miR-101-2 expression might represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic (HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis (M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and the 7924 potential target genes from the prediction databases. These genes were related to transcription, metabolism, biosynthesis, and proliferation. The results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt, and chemokine signaling pathways.ConclusionsMiR-101-1 and miR-101-2 may be prospective biomarkers for the prognosis and diagnosis of BC, respectively, and are associated with diverse clinical parameters. The target genes of miR-101-3p regulate the development and progression of BC. These results provide insight into the pathogenic mechanism and potential therapies for BC.
PurposeTo investigate the clinicopathological value and potential roles of microRNA-198 (miR-198) in hepatocellular carcinoma (HCC).MethodsNinety-five formalin-fixed paraffin-embedded HCC and the para-cancerous liver tissues were gathered. Real-time reverse transcription quantitative polymerase chain reaction was applied to determine the miR-198 expression. The association between the miR-198 expression and clinicopathological features was examined. Meanwhile, potential target messenger RNAs of miR-198 in HCC were obtained from 14 miRNA prediction databases and natural language processing method, in which we pooled the genes related to the tumorigenesis and progression of HCC and classified them by their frequency. The selected target genes were finally analyzed in the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway.ResultsmiR-198 expression was significantly lower in HCC than that in adjacent noncancerous liver tissues (1.30±0.72 vs 2.01±0.58, P<0.001). Low miR-198 expression was also correlated to hepatitis C virus infection (r=−0.48, P<0.001), tumor capsular infiltration (r=−0.43, P<0.001), metastasis (r=−0.26, P<0.010), number of tumor nodes (r=−0.25, P=0.013), vaso-invasion (r=−0.24, P=0.017), and clinical tumor node metastasis stage (r=−0.23, P=0.024). Altogether, 1,048 genes were achieved by the concurrent prediction from at least four databases and natural language processing indicated 1,800 genes for HCC. Further, 127 overlapping targets were further proceeded with for pathway analysis. The most enriched Gene Ontology terms in the potential target messenger RNAs of miR-198 were cell motion, cell migration, cell motility, and regulation of cell proliferation in biological process; organelle lumen, membrane-enclosed lumen, and nuclear lumen in cellular component; and enzyme binding, protein domain-specific binding, and protein kinase activity in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis showed that these target genes were obviously involved in focal adhesion and pathways in cancer.ConclusionLower expression of miR-198 was related to several clinicopathological parameters in HCC patients. miR-198 might play a regulatory role through its target genes in the development of HCC.
Lymph node metastasis commonly occurs in gastric cancer. Previous studies have demonstrated that the overexpression of lymphatic microvessel density (LVD) is correlated with various malignancies. To evaluate the potential role of LVD in various malignancies, we conducted a systematic review and meta-analysis to thoroughly investigate the association of LVD expression with tumor progression and survival in gastric cancer. We performed a comprehensive search of common databases and selected studies demonstrating the relationship between LVD expression and gastric cancer prognosis. Hazard ratios (HR) were used to determine the value of LVD for predicting gastric cancer metastasis and prognosis. The data were extracted from the included studies and pooled with the appropriate effects model using STATA 12.0. The results showed that high LVD expression obviously impacted the prognosis of gastric cancer, based on an overall survival (OS) HR of 2.58 (95% CI: 1.91–3.48, P < 0.001) and a disease-free survival (DFS) HR of 2.51 (95% CI: 1.35–4.68, P = 0.004) in the univariate analysis. In addition, the results of the multivariate analysis indicated a remarkable relationship between high LVD expression and gastric neoplasm prognosis. The pooled OS HR was 4.12 (95% CI: 3.45–4.91, P < 0.001). The current meta-analysis shows that high LVD is closely related to tumor metastasis and poor prognosis in gastric malignancy. LVD could be a key factor in tumor lymphatic metastasis. Moreover, LVD is likely a potential index and an effective biomarker for the prediction of patient prognosis.
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