RESUMO
BACKGROUND: Accumulating evidence demonstrates that microRNAs (miRNAs) play essential roles in tumorigenesis and cancer progression of hepatocellular carcinoma (HCC). Average targets of a miRNA were more than 100. And one miRNA may act in tumor via regulating several targets. The present study aimed to explore more potential targets of miR-449a by proteomics technology and further uncover the role of miR-449a in HCC tumorigenesis. METHODS: Technologies such as iTRAQ-based quantitative proteomic were used to investigate the effect of miR-449a on HCC. The expression of c-Met and miR-449a was detected by qRT-PCR in HCC samples. Gain- and loss-of-function experiments were performed to identify the function and potential target of miR-449a in HCC cells. RESULTS: In HCC, miR-449a was significantly downregulated, while c-Met was upregulated concurrently. Quantitative proteomics and luciferase reporter assay identified c-Met as a direct target of miR-449a. Moreover, miR-449a inhibited HCC growth not only by targeting CDK6 but also by suppressing c-Met/Ras/Raf/ERK signaling pathway. Furthermore, the inhibition of c-Met expression with a specific siRNA significantly inhibited cells growth and deregulated the ERK pathway in HCC. CONCLUSION: The tumor suppressor miR-449a suppresses HCC tumorigenesis by repressing the c-Met/ERK pathway.
Assuntos
Carcinoma Hepatocelular/enzimologia , Proliferação de Células , Pontos de Checagem da Fase G1 do Ciclo Celular , Fator de Crescimento de Hepatócito/metabolismo , Neoplasias Hepáticas/enzimologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento de Hepatócito/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-met/genética , Transdução de Sinais , Células Tumorais CultivadasRESUMO
BACKGROUND: Laparoscopic gastrectomy (LG) has been widely applied in patients with gastric cancer (GC). However, the safety and application value of LG in elderly patients with GC was still unclear. In this study, we aimed to evaluate the feasibility and safety of LG for elderly patients with GC using the meta-analysis. METHODS: Studies comparing elderly patients and nonelderly patients who underwent LG for GC were reviewed and collected from the PubMed, EBSCO, Cochrane Library, and EMBASE. Outcomes such as operative results, postoperative recovery, and morbidity were compared and analyzed. The Review Manager 5.3 was used to portray the weighted mean difference (WMD) and odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Eleven observational studies with a total of 3275 patients were included. Compared with nonelderly patients, elderly patients had shorter operation time (WMD -10.46; 95% CI -17.06 to -3.86; Pâ=â.002), less retrieved lymph nodes (WMD -2.34; 95% CI -3.77 to -0.92; Pâ=â.001), delayed time to first flatus (WMD 0.31; 95% CI 0.10-0.51; Pâ=â.003), longer postoperative hospital stays (WMD 1.06; 95% CI 0.07-2.05; Pâ=â.04), higher risk for overall postoperative complication (OR 1.34; 95% CI 1.08-1.67; Pâ=â.009), nonsurgical postoperative complication (OR 1.98; 95% CI 1.24-3.15; Pâ=â.004), and postoperative pulmonary complication (OR: 3.09; 95% CI 1.68-5.68; Pâ<â.001). There was no significance between nonelderly patients and elderly patients regarding the estimated blood loss, incidences of surgical postoperative complication, surgical site infection, and ileus (Pâ>â.05). CONCLUSION: Outcomes of LG for elderly patients were comparable to those in nonelderly patients. Age alone should not preclude LG in elderly patients.