RESUMO
Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with cancer risk and disease outcome. We evaluated the predictive value of these SNPs for GEP-NEN outcome. Three SNP sites of nucleotides 16257C/A, 150C/T and 151C/Tdel were identified for statistically significant prediction of postoperative survival in GEP-NEN by univariate analysis with log-rank test. In addition, the minor haplotype of nucleotides 16257A in the hypervariable segment 1(HV1) region of the D-loop was identified for their association with lower survival rate of GEP-NEN (relative risk, 3.390; 95% CI, 1.071~10.729; p=0.038) by multivariate analysis with COX hazards model. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups with a high risk of GEP-NEN outcome.
Assuntos
DNA Mitocondrial/genética , Neoplasias Intestinais/genética , Neoplasias Intestinais/mortalidade , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
Previous studies indicate that microRNA-122 (miR-122) is down-regulated in several cancer cells and regulates cell apoptosis, proliferation, metastasis, and tumor angiogenesis. However, the mount of miR-122 in bladder cancer and the pivotal molecular mechanisms of miR-122 used to regulate bladder carcinogenesis and angiogenesis remain to be clarified. Here, we reveal that miR-122 expression is down-regulated in human bladder cancer tissues and cell lines. MiR-122 represses vascular endothelial growth factor C (VEGFC) post-transcriptional expression by directly binding to its 3'-UTR. The protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which are the most important downstream molecules of VEGFC, are also decreased in bladder cancer cell after miR-122 overexpression. Furthermore, miR-122 over-expression decreases bladder cancer cell migration, invasion, colony formation in vitro and slow bladder cancer growth and angiogenesis in vivo. Finally, miR-122 sensitizes bladder cancer cells to cisplatin-induced apoptosis. Taken together, these studies suggest that miR-122 serves as a tumor suppressor and down-regulating VEGFC expression, leading to the inhibition of bladder cancer growth and angiogenesis.