RESUMO
MicroRNAs are a class of ≈22-nt noncoding single-strand RNAs regulating gene expression postscriptionally. Metastasis caused poor prognosis in colorectal cancer patients and half of the patients developed metastatic lesions when admission. Here we investigated the possible roles of microRNAs in regulating metastasis in the paired colon cancer cells SW480 and SW620. Among those dysregulated microRNAs, miR-200c was speculated to inhibit metastasis by targeting ZEB1. Overexpression of miR-200c was concurrent with downregulation of ZEB1 mRNA and protein. Functional assays demonstrated that modulation of miR-200c with mimics or inhibitors changed potential of metastasis in SW480/620 cancer cells in vitro. Taken together, our study demonstrated that miR-200c inhibits metastatic ability by targeting ZEB1 in colon cancer cells SW480/620 and suggested that modulation of miR-200c could serve as therapeutic tool for inhibiting metastasis in colorectal cancer.
Assuntos
Movimento Celular , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Fatores de Transcrição/genética , Western Blotting , Adesão Celular , Linhagem Celular Tumoral , Proteínas de Homeodomínio/metabolismo , Humanos , Invasividade Neoplásica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de ZincoRESUMO
BACKGROUND: We performed a meta-analysis to evaluate the efficacy and safety of Fluorouracil (FU)/Leucovorin (LV)/Oxaliplatin compared to FU/LV in treating advanced colorectal cancer. METHODS: Two independent researchers identified and extracted all relevant literature using MEDLINE and the Cochrane Library Database. The regimens included arm A (FU/LV) and arm B (FU/LV/Oxaliplatin) with no other chemotherapy agent. RESULTS: Five randomized controlled trials (RCTs) fulfilled the requirements. All RCTs showed superiority of FU/LV/Oxaliplatin to FU/LV when measuring RR (response rate) and PFS (progression-free survival); no significant improvement in OS (overall survival) was observed. This meta-analysis shows a better RR for the FU/LV/Oxaliplatin group (OR 4.02, 95% CI 2.37-6.82, p<0.00001). The incidence of grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, neurological toxicity, toxicity-related dose modification and discontinuation was higher in the FU/LV/Oxaliplatin group, while the incidence of anemia, nausea and diarrhea was not different. CONCLUSION: FU/LV/Oxaliplatin offers better efficacy (RR and PFS) than FU/LV in the treatment of advanced colorectal cancer. The incidence of grade 3/4 toxicities, i.e. neutropenia, thrombocytopenia, vomiting, neurological toxicity, is significantly higher in the FU/LV/Oxaliplatin than in the FU/LV group but these are manageable or reversible.
