Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

摘要: Cancer-associated fibroblasts (CAFs) are the main component of tumor stroma and promote progression through several mechanisms. Recent evidence indicates that small noncoding RNAs, microRNAs (miRNAs), play key roles in CAF tumor-promoting properties; however, role miRNAs lung cancer-associated remains poorly defined. We characterized differential miRNA expression profile isolated from matched front (F-CAFs), inner (In-CAFs), normal adjacent (NFs) tissues four adenocarcinoma patients (ADs) using microarray analysis. Proliferation invasion assays A549 human cancer cells presence conditioned medium F-CAFs, In-CAFs or NFs were performed to assess tumorigenic properties. Ten identified candidate 12 ADs then validated by RT-PCR. Both F-CAFs enhanced proliferation compared with NFs; moreover, showed a significantly stronger effect than In-CAFs. RT-PCR validation demonstrated three downregulated (miR-145-3p, miR-299-3p, miR-505-3p), two (miR-410-3p miR-485-5p), but no differentially expressed between NFs. Further target-gene prediction pathway enrichment analysis indicated deregulated significant associations "pathways cancer" miR-299-3p miR-410-3p), "Wnt signaling pathway" "TGF-beta (miR-410-3p). Importantly, growth factor targeted those miRNAs, VEGFA, was upregulated NFs, as judged In conclusion, potentially associated