RESUMO
INTRODUCTION: MicroRNAs (miRNAs) play important roles in tumorigenesis. In this study, we investigated the role of miR-221 in the development and progression of clear cell renal cell carcinoma (ccRCC). METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-221 in ccRCC tissues and cell lines. Then, we investigated the role of miR-221 to determine its potential roles on renal cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-221 and the results were validated in renal cancer cells. RESULTS: In the present study, we found that miR-221 was significantly increased in ccRCC tissues and cell lines. Knocked-down expression of miR-221 remarkably inhibited cell proliferation, migration and invasion of renal cancer cells. Moreover, at the molecular level, our results suggested that TIMP2 as a direct target of miR-221 through which miR-221 promoted tumor cell proliferation, migration and invasion. CONCLUSIONS: These findings suggested that miR-221 play an oncogenic role in the renal cancer cell proliferation, migration and invasion by directly inhibiting the tumor suppressor TIMP2, indicating miR-221 act as a potential new therapeutic target for the treatment of ccRCC.
Assuntos
Carcinoma de Células Renais/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Renais/metabolismo , MicroRNAs/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Regiões 3' não Traduzidas , Sítios de Ligação , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Genes Reporter , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/genética , Invasividade Neoplásica , Oncogenes , Interferência de RNA , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-2/genética , TransfecçãoRESUMO
BACKGROUND: We analyzed a database from our hospital comprised of 31 cases of primary breast lymphoma (PBL) that included treatment and follow-up information during the past 30 years, and investigated the correlation between microvessel density (MVD) and survival in patients with PBL. PATIENTS AND METHODS: We reviewed all patients diagnosed with primary breast lymphoma from June 1977 to March 2007. Patient demographics such as survival, recurrence, and time to follow-up were recorded, in addition to surgical, radiation, and/or chemotherapy treatment(s). We also assessed microvessel density (MVD) in the pretreatment breast lump of 31 previously untreated patients using α-CD34 immunohistochemical staining. RESULTS: All 31 patients were female ranging in age from 37 years to 75 years. Diffuse large B-cell lymphoma was the most common histologic diagnosis. According to the staging of Wiseman and Liao, 17 patients (55%) were stage IE, and 14 patients (45%) were stage IIE. Treatment that included radiation therapy in stage I patients (node negative) improve the survival rate and lowered the recurrence rates. Treatment that included chemotherapy in stage II patients (node positive) showed benefits in terms of higher survival rate and lower recurrence rate. Increasing microvessel density is a weak but statistically significant predictor of lower survival overall. CONCLUSION: Nodal status predicts the outcome and guides the use of radiation and chemotherapy. There is no statistical difference between the different types of operative methods. Patients with high MVD measured in the microenvironment had worse survival overall than PBL patients with low expression.