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1.
Eur Rev Med Pharmacol Sci ; 23(4): 1418-1427, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30840262

RESUMO

OBJECTIVE: Long non-coding RNA DBH-AS1 (DBH-AS1) has emerged as a novel regulator in cancer initiation and progression of several tumors. However, the expression of DBH-AS1 in osteosarcoma and its effect on the tumorigenesis of osteosarcoma are unclear. The purpose of this study was to determine the role of DBH-AS1 in osteosarcoma progression. PATIENTS AND METHODS: The expression level of DBH-AS1 in 119 pairs of osteosarcoma tissues and five cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association of DBH-AS1 expression with clinicopathological factors and prognosis was also analyzed. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8), EdU and cell colony formation assays and apoptosis in MG63 and U2OS cells was examined by flow cytometry. Following that, transwell invasion and wound-healing assays were used to explore cell migration and invasion, respectively. The expression of the PI3K/Akt pathway-related proteins was examined by Western blot analysis. RESULTS: We observed that DBH-AS1 was distinctly overexpressed in osteosarcoma tissue and cells, and associated with lymph node status and metastasis status. Osteosarcoma patients with a higher DBH-AS1 expression showed significantly poorer overall survival than those with lower DBH-AS1 expression. Multivariate analysis demonstrated that high DBH-AS1 expression was an independent poor prognostic factor for osteosarcoma patients. Functional assays revealed that knockdown of DBH-AS1 inhibited cell proliferation, migration and invasion, while promoted apoptosis in osteosarcoma. Moreover, suppression of DBH-AS1 could inhibit the activation of the PI3K/Akt pathway, which was demonstrated by examining the expression levels of p-PI3K and p-Akt. CONCLUSIONS: Our data first reported that DBH-AS1 may act as an oncogenic lncRNA by modulating the PI3K/Akt pathway in osteosarcoma, which may serve as a candidate prognostic biomarker and target for new therapies in osteosarcoma.


Assuntos
Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Osteossarcoma/genética , Osteossarcoma/mortalidade , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Taxa de Sobrevida
2.
Eur Rev Med Pharmacol Sci ; 22(1): 135-141, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29364480

RESUMO

OBJECTIVE: To investigate the correlations of the computed tomography (CT) signs of non-small cell lung cancer (NSCLC) with pathological features and the expression levels of phosphoprotein 53 (p53) and c-Myc in patients. PATIENTS AND METHODS: 87 patients with NSCLC admitted to the Department of Oncology in our hospital from July 2014 to March 2017 were randomly selected. Morphologies of NSCLC and cancer-adjacent tissues were detected by hematoxylin and eosin (H&E) staining; messenger ribonucleic acid (mRNA) and protein levels of p53 and c-Myc in cancer and cancer-adjacent tissues were detected using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC); spiral CT (SCT) was conducted for exploring imaging signs of patients with NSCLC; the correlation of CT signs with pathology and the expressions of p53 and c-Myc was analyzed. RESULTS: H&E staining showed that NSCLC tissues had a larger nucleus, a larger nucleus-cytoplasm ratio, and a more evident histopathological atypia, with no clear histological structure compared with cancer-adjacent normal tissues; RT-PCR and IHC results revealed that the mRNA and protein expression levels of p53 and c-Myc in NSCLC tissues were significantly higher than those in cancer-adjacent tissues, in which differences in mRNA levels were 1.75 folds and 1.84 folds, respectively (p<0.05). SCT signs indicated that swollen lymph nodes and spiculation, spinous process and deep lobulation signs often occurred in the chest of NSCLC patients, and pleural indentation appeared in the majority of patients; the chi-square test results showed that the positive rates of p53 and c-Myc proteins were not related to pathological types of NSCLC, but significantly correlated with tumor differentiation (p<0.05); the positive rates of p53 and c-Myc proteins were correlated with tumor diameter, spiculation and deep lobulation signs and lymph node metastasis (p<0.05), but not associated with spinous process, vacuole and pleural indentation signs (p>0.05). CONCLUSIONS: CT scan combined with the detection of p53 and c-Myc expressions can improve the diagnosis of lymph node metastasis and clinical staging for patients with NSCLC, which is conducive to the clinical treatment and prognosis analysis of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/metabolismo , Tomografia Computadorizada por Raios X , Proteína Supressora de Tumor p53/genética
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