RESUMO
Previous studies demonstrated that the acquired drug resistance of non-small cell lung cancer (NSCLC) was related to deregulation of miRNAs. However, the effects of miR-107 and the mechanism through which miR-107 affects the cisplatin chemoresistance in NSCLC have not been reported. TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-107 and cyclin dependent kinase 8 (CDK8) protein. The viabilities of treated cells were analyzed using MTT assay. We found that the expression level of miR-107 in A549 cells was significantly lower than that in normal human bronchial epithelial cells (0.45 ± 0.26 vs. 1.00 ± 0.29, P = 0.032). The MTT assay showed that the A549 cells transfected with miR-107 mimics were significantly more sensitive to the therapy of cisplatin than control cells. A549 cells transfected with miR-107 mimics showed a decreased CDK8 protein expression. Downregulation of CDK8 expression by siRNAs, A549 cells became more sensitive to the therapy of cisplatin. In addition, the enhanced growth-inhibitory effect by the miR-107 mimic transfection was enhanced after the addition of CDK8 siRNA. In conclusion, the present study provides the first evidence that miR-107 plays a key role in cisplatin resistance by targeting the CDK8 protein in NSCLC cell lines, suggesting that miR-107 can be used to predict a patient's response to chemotherapy as well as serve as a novel potential maker for NSCLC therapy.
Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Cisplatino/farmacologia , Quinase 8 Dependente de Ciclina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/enzimologia , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 8 Dependente de Ciclina/genética , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Interferência de RNA , TransfecçãoRESUMO
OBJECTIVE: To study the survival and prognostic implication in surgically resected satellite-nodule T4 (T4 satellite) non-small cell lung cancer (NSCLC). METHODS: From January 1995 to March 2005, the complete resection was performed to 42 patients with NSCLC who were postoperatively identified as pathologic-stage T4 satellite. Survival and associations between clinicopathological parameters and prognosis were analyzed. Thirty-two patients with pathologic stage local-invasion T4 (T4 invasion) NSCLC who underwent resection at the same time were also analyzed. RESULTS: The 1-, 3- and 5-year survival was 76.2%, 57.1% and 46.0% for patients with T4 satellite, while 62.3%, 31.5% and 20.0% for patients with T4 invasion. There was a significant higher survival in T4 satellite group when compared to that in T4 invasion group (P < 0.05). Furthermore, patients with T4 satellite N0M0 got a better survival than those with T4 satellite N1-2M0, T4 invasion N0M0 and T4 invasion N1 -2M0 (P < 0.05). For patients with T4 satellite, univariate analysis showed that histology, main tumor size, lymph node status and adjuvant chemotherapy were linked with survival, while main tumor size, lymph node status and adjuvant chemotherapy served as the independent prognostic factors with multivariate analysis. CONCLUSIONS: Patients with completely resected T4 satellite NSCLC have a better prognosis than those with T4 invasion. Main tumor size over 3 cm, lymph node metastasis or no adjuvant chemotherapy means an unfavorable prognosis.
