RESUMO
Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Regiões 3' não Traduzidas/genética , Células A549 , Apoptose/genética , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Análise de Regressão , Transdução de Sinais , Regulação para Cima/genéticaRESUMO
BACKGROUND: Active tuberculosis (TB) with negative results of sputum smear is difficult to be identified. Till now, there is no effective and noninvasive diagnostic method. This study evaluated the diagnostic power of Mycobacterium tuberculosis T-cell (T.SPOT®.TB) assays for active TB. METHODS: We retrospectively screened 450 suspected TB patients that were hospitalized in the Respiratory Department of Henan Province People's Hospital from June 2015 to June 2016. The patients were divided into the active, previous, and non-TB groups according to their final diagnosis. We evaluated the diagnostic value of the T-SPOT®.TB assay by constructing receiver operating characteristic (ROC) curves and calculating the optimal diagnostic cutoff value. In addition, we compared the levels of A antigen (ESAT-6) and B antigen (CFP-10) in active TB. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of T-SPOT®.TB for active TB were 89.78%, 63.16%, 0.56, 0.92, 2.47, and 0.16, respectively. For active TB, the area under the ROC curve (AUC) of the A antigen (0.89) was higher than that of the B antigen (0.86). The AUC of the A antigen for active TB was largest at a cutoff value of 13.5 spot-forming cells (SFCs) per 2.5 × 105 peripheral blood mononuclear cells (PBMCs). The AUC of the A and B antigens was 0.60 and 0.58 for previous TB. The levels of A and B antigen in the active TB group were significantly different from those in the previous- and non-TB groups (A antigen: χ2 = 105.41, P< 0.01 and B antigen: χ2 = 91.03, P< 0.01; A antigen: χ2 = 12.99, P< 0.01 and B antigen: χ2 = 8.56, P< 0.01, respectively). There were no significant differences in the levels of A and B antigens between the non-TB group and previous TB group (A antigen: χ2 = 1.07, P> 0.05 and B antigen: χ2 = 0.77, P> 0.05). CONCLUSIONS: T-SPOT®.TB has high sensitivity and specificity for the diagnosis of active TB at a cutoff value of 13.5 SFCs per 2.5 × 105 PBMCs and is not influenced by previous TB.