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Biomed Pharmacother ; 86: 248-253, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28006750


Previous studies showed that miR-382 plays important roles in several types of cancers. Nevertheless, its expression and function in non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that miR-382 expression was evidently downregulated in NSCLC tissue and cell lines in comparison with the adjacent normal tissues and human bronchial epithelial cell line (16HBE). Moreover, the expression levels of miR-382 were significantly associated with last-stage and tumor metastasis in NSCLC patients. In addition, exogenous miR-382 evidently inhibited NSCLC cell proliferation, migration and invasion in vitro. We also revealed SETD8 as a direct target of miR-382 in NSCLC, and restored SETD8 partially reversed the negative effects miR-382 on NSCLC cells. In total, our study demonstrated that miR-382 dysregulated in NSCLC and involved in NSCLC tumorigenesis and metastasis by suppressing SETD8 expression, which may help to identify effective therapies for NSCLC treatment.

Carcinoma Pulmonar de Células não Pequenas/genética , Marcação de Genes/métodos , Histona-Lisina N-Metiltransferase/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Feminino , Histona-Lisina N-Metiltransferase/biossíntese , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/administração & dosagem , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle
DNA Cell Biol ; 35(12): 751-757, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27661766


Klotho is originally discovered as an anti-aging gene and recently identified as a tumor suppressor in various human cancers. Drug resistance is a major obstacle to affect the treatment of chemotherapy. In the present study, we explore the role of klotho on drug resistance in human lung cancers and investigate the mechanism of klotho on drug resistance in lung cancer cells. First, we detected a panel of six human lung cancer cell lines, including H460, SK-MES-1, cisplatin (DDP)-resistant A549/DDP, its parental subline A549, docetaxel (DTX)-resistant SPC-A-1/DTX, and SPC-A-1 by western blotting analysis. The results showed that klotho level was significantly decreased in chemotherapeutic drug-resistant lung cancer cells. Next, klotho was overexpressed in drug-resistant cancer cell lines and the results showed that overexpression of klotho significantly inhibited cell proliferation of A549/DDP and SPC-A-1/DTX. Conversely, knockdown of the expression of klotho significantly promoted cell growth of lung cancer cells. Furthermore, overexpression of klotho had synergistic effects with cisplatin to inhibit the proliferation of drug-resistant lung cancer cells in a dose- and time-dependent manner. The molecular mechanism was explored by western blotting analysis and the results revealed that the levels of beclin 1 and LC3-II were obviously increased, suggesting cell autophagy enhanced in drug-resistant cancer cells. Importantly, overexpression of klotho would inhibit cell autophagy in A549/DDP cells. All the results demonstrated that the levels of klotho were significantly decreased, which was accompanied by the increased cell autophagy in drug-resistant lung cancer cells. Overexpression of klotho would inhibit cell autophagy in drug-resistant lung cancers, which may probably contribute to reverse drug resistance in lung cancer cells.

Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Glucuronidase/genética , Mucosa Respiratória/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Docetaxel , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Humanos , Especificidade de Órgãos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Transdução de Sinais , Taxoides/farmacologia , Transgenes
Biochem Biophys Res Commun ; 437(1): 108-13, 2013 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-23806693


Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.

Proteínas Culina/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Culina/genética , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , Fosforilação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(7): 675-8, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20619092


AIM: To approach the relationships among inflammation, immune response, and fibrosis in combined pulmonary fibrosis and emphysema (CPFE) through the observation of distributions of lymphocyte subtypes, the variation of Pro-collagen III N-terminal peptide (PIIINP) expression and the severity of pulmonary fibrosis (PF) in CPFE. METHODS: From March 2005 to March 2007, 21 diagnosed cases of CPFE, 25 diagnosed cases of idiopathic pulmonary fibrosis (IPF) and 19 cases of controls were involved in the study from the First Affiliated Hospital of Xi'an Jiaotong University. The patients were subjected to the following investigations including pathological changes in lung tissue biopsy specimens by light microscopy, counting and classification of inflammatory cells out of bronchoalveolar lavage fluids (BALF), determination of T-lymphocyte subtypes by flow cytometry (FCM), and detection of PIIINP level in BALF and blood serum by radioimmunoassay. RESULTS: The pathological data showed higher degree of fibrosis in IPF group than that in CPFE group (P<0.01), but the level of fibrosis in the two Zgroups had nothing to do with smoking status (P>0.05). The inflammatory cells and lymphocyte cells in BALF were more in CPFE group than those in IPF and control groups (P<0.05, P<0.01 respectively). The FCM showed CPFE group had more CD8+ T-lymphocytes than IPF and control groups (P<0.05), whereas CPFE and IPF groups showed significantly lower CD4+/CD8+ ratio than the control group (P<0.01). There was no significantly statistical difference in the percentage of CD4+ T-lymphocytes among the three groups (P>0.05). CPFE and IPF groups exhibited significantly higher level of blood PIIINP than the control group (P<0.01), while IPF group showed markedly higher level of blood PIIINP than CPFE group (P<0.01). BALF and blood level of PIIINP were positively correlated (gamma=0.82). CONCLUSION: The pulmonary fibrosis in CPFE shows intrinsic characteristics, with smoking not being the major or direct PF-driven factor. The CPFE group showed significant inflammation predominated by T-lymphocytes, especially CD8+; T-lymphocyte, as compared with the IPF and control groups, hence pointing to the fact that a novel anti-lymphocytes and immune regulation strategy may be useful for disease intervention. Blood serum PIIINP may be used as a marker for early detection of CPFE and also as a monitor for efficacy of treatments.

Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Enfisema Pulmonar/imunologia , Fibrose Pulmonar/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Pró-Colágeno/imunologia , Enfisema Pulmonar/sangue , Enfisema Pulmonar/patologia , Fibrose Pulmonar/sangue , Fibrose Pulmonar/patologia , Adulto Jovem