RESUMO
Cutaneous melanoma is an aggressive neoplasm and is responsible for the majority of skin cancer deaths. Several miRNAs are involved in melanoma tumor progression. One of them is miR-205, the loss of which contributes to the development of melanoma metastasis. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis identified 243 differentially expressed transcripts including inositol polyphosphate 5'-phosphatase-like protein-1 (INPPL1) and BTB/POZ Domain-Containing Protein 3 (BTBD3). INPPL1 and BTBD3 were downregulated when melanoma cells expressed miR-205, indicating that these genes are potential miR-205 targets. Additionally, the target prediction algorithm TargetScan revealed that INPPL1 and BTBD3 genes had predicted target sites of miR-205 in their 3'UTRs and functional analysis demonstrated that these genes were directly linked to miR-205. Interestingly, our clinical data showed that INPPL1 was significantly associated with lymph node metastasis-free survival (LNMFS), distant metastasis-free survival (DMFS) and melanoma specific survival (MSS). This study supports INPPL1 as a miR-205 target gene and, therefore, that the involvement of miR-205 in the metastatic dissemination of malignant melanoma is, at least in part, via INPPL1.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Metástase Linfática/genética , Melanoma/genética , Melanoma/patologia , MicroRNAs/genética , MicroRNAs/fisiologia , Metástase Neoplásica/genética , Proteínas do Tecido Nervoso/economia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Transcriptoma/genética , Regiões 3' não Traduzidas/genética , Intervalo Livre de Doença , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Humanos , Melanoma/mortalidade , Proteínas do Tecido Nervoso/genética , Neoplasias Cutâneas/mortalidade , Células Tumorais CultivadasRESUMO
Aims.Bifidobacterium pseudocatenulatum CECT 7765 improves metabolic and immunological altered functions in high fat fed mice, however little is known about the effects of potential probiotics on vascular reactivity. The aim of the present study was to investigate the effects of a potential probiotic strain, Bifidobacterium pseudocatenulatum CECT 7765, on vascular response in obese mice. Methods. Aorta samples were obtained from mice, which were divided into three groups: a control group, receiving a standard diet; an obese group, receiving a high-fat diet; and an obese group receiving high-fat diet and a daily dose of B. pseudocatenulatum CECT 7765 by oral gavage. Aortic rings were suspended in organ baths for isometric recording of tension. mRNA expression of eNOS was evaluated by real-time polymerase chain reaction. Results. Contractions induced by KCl, noradrenaline and thromboxane analogue were 33%, 30% and 45% lower respectively in aortic rings from obese mice. Bifidobacteria administration reversed this effect. eNOS inhibition increased the response to noradrenaline in the three groups with a significant lower magnitude in aortic rings from obese mice receiving bifidobacteria supplement. Acetylcholine caused a greater vasodilation in aorta from obese group (46±3% for control and 69±4% for obese group; p<0.05) and bifidobacteria reversed it (57±5%). Response to sodium nitroprusside was displaced 2.9 times to the left in a parallel manner in obese group. Relaxation to sodium nitroprusside remained unchanged in the bifidobacteria fed group. There was about five-fold decreased mRNA expression of eNOS in aortic segments from the group receiving bifidobacteria. Conclusion.Bifidobacterium pseudocatenulatum CECT 7765 restores the obesity-induced altered vascular function mainly by reducing nitric oxide release.