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[This corrects the article DOI: 10.3892/ol.2017.6106.].
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The ubiquitin proteasome pathway is conserved from yeast to mammals and is necessary for the targeted degradation of most short-lived proteins in eukaryotic cells. Its protein substrates include cell cycle regulatory proteins and proteins that are not properly folded in the endoplasmic reticulum. Owing to the ubiquity of its protein substrates, ubiquitination regulates a variety of cellular activities, including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune response. With new genomic data continuously being obtained, ubiquitination through genomic data analysis will be an effective method. We obtained 83 overlapping genes from four glioma databases, which differed from ubiquitin ligase Nrdp1 expression, including 36 downregulated and 47 upregulated genes. The KEGG pathways, molecular functions, cellular components, and biological processes potentially associated with Nrdp1 were obtained using GSEA and Cytoscape. In human gliomas, differences in the expression of Nrdp1 were identified between nontumor brain tissue and different glioma tissues, but no difference in expression was found between lowgrade glioma (LGG) and anaplastic glioma (AG). In survival analysis, we found no significant association between Nrdp1 expression level and patient prognosis.
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Neoplasias Encefálicas/genética , Bases de Dados de Proteínas , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Ubiquitina-Proteína Ligases/genética , Biologia Computacional , Dano ao DNA , Reparo do DNA , Humanos , Sistema Imunitário , PrognósticoRESUMO
Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.
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Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioma , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/biossíntese , RNA não Traduzido/biossíntese , Proteínas Adaptadoras da Sinalização Shc/biossíntese , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Intervalo Livre de Doença , Feminino , Glioma/metabolismo , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
The ubiquitin ligase ring finger protein 5 (RNF5) has previously been associated with the development of breast cancer. Patients with breast cancer and high RNF5 expression have been demonstrated to have a shorter survival time compared with patients with low RNF5 expression. However, the role of RNF5 in human glioma has not been determined. The present study analyzed the role of RNF5 in gliomas using bioinformatics analysis. The results revealed that RNF5 was differentially expressed in non-cancerous brain tissues and different grades of glioma. Furthermore, a high RNF5 expression in patients with glioma was associated with an improved prognosis compared with patients with low expression. Gene Set Enrichment Analysis revealed that RNF5 was particularly associated with 'Wnt signaling pathway', 'apoptosis', 'focal adhesion' and 'cytokine-cytokine receptor interaction' in patients with glioma. Additionally, 4 potential ubiquitination substrates for RNF5 were predicted, including sorting nexin 10, proprotein convertase subtilisin/kexin type 1, leucine rich glioma inactivated 1 and solute carrier family 39 member 12. These findings provided the basis for further investigation on the role of RNF5 in tumors.
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The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably. Cacybp forms a complex with the E3 ubiquitinated ligase Siah1 to participate in ubiquitination. We analyzed Cacybp-associated genes using the Gene Expression Omnibus (GEO) and CGGA (Chinese Glioma Genome Atlas) databases and identified 121 differentially expressed genes (DEGs), of which 46 were downregulated and 75 were upregulated. The biological processes, molecular functions, and protein-protein interaction (PPI) network of differential genes were analyzed by Cytoscape software and STRING software. We found no difference in Cacybp expression among different grades of gliomas and there was no significant association between the expression level of Cacybp and the prognosis of patients with glioma in LGG and GBM. © 2019 IUBMB Life, 1-8, 2019.
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Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioma/metabolismo , Proteínas de Ligação ao Cálcio/genética , Bases de Dados Factuais , Feminino , Perfilação da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Taxa de SobrevidaRESUMO
Osteosarcoma is the most common primary malignant bone tumor type in children and adolescents under 20 years of age. Biological characteristics include invasiveness, metastasis, abnormal differentiation and loss of contact inhibition. microRNAs (miRNAs) are involved in the transcriptional and post-transcriptional regulation of target mRNAs. Previous studies have demonstrated that miR-218 inhibits tumor formation and progression in glioma, colon cancer and renal cell carcinoma; however, the mechanism of action of miR-218 in osteosarcoma has not been completely determined. In the present study, it was demonstrated that miR-218 exhibited low expression and targeted E2F2 in osteosarcoma cells. Additionally, overexpression of miR-218 inhibited osteosarcoma cell proliferation, with the opposite result occurring following the knockdown of miR-218. Furthermore, it was determined that miR-218 inhibited tumor formation and reduced the expression of E2F2 and proliferating cell nuclear antigen in nude mice. Collectively, the present data demonstrated that miR-218 serves an important role in suppressing the proliferation of osteosarcoma cells, potentially regulated by E2F2, which may provide a novel protein marker for the treatment of osteosarcoma.
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Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy. Despite therapeutic advancements, relapse of the pathological state in the form of central nervous system (CNS) disease remains a challenge. CNS disease appears to be present at diagnosis in at least 40% of patients. This relapse in the form of CNS disease is one of the major hurdles in achieving complete cure. The present review article aims to discuss the important mechanisms of leukemic entry and infiltration patterns of leukemic cells into the CNS. Also, latest updates in the management strategies of ALL will also be focused in the present article.
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Neoplasias do Sistema Nervoso Central/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Resultado do TratamentoRESUMO
The most common type cancer prevailing in pediatric patients worldwide is acute lymphoblastic leukemia (ALL). The characteristic feature of this cancer is the accumulation of immature lymphoid cell in the bone marrow. Further a subtype of ALL namely B-cell precursor (BCP)-ALL has raised in the recent years and is the most common subtype of ALL prevalent in children worldwide. The present review article will put light on the current aspects of BCP ALL including etiology, causative factors, diagnostic and treatment.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , PrevalênciaRESUMO
RATIONALE: Childhood chronic myeloid leukemia (CCML) is a malignant disease of granulocyte abnormal hyperplasia that is caused by clonal proliferation of pluripotent stem cells. The condition is relatively rare, accounting for 2.0% to 3.0% of cases of childhood leukemia. In addition, the incidence of extramedullary blast crisis in CCML presenting as central nervous system (CNS) blast crisis remaining chronic phase of the disease in bone marrow is extremely unusual. PATIENT CONCERNS: We report a case of childhood chronic myelogenous leukemia that abandoned treatment, resulting in chronic myelogenous leukemia transforming into extramedullary blast crisis resulting in CNS leukemia, accompanied by the chronic phase of the disease in bone marrow. DIAGNOSES: Chronic myeloid leukemia extramedullary blast crisis presenting as CNS leukemia without blast crisis in bone marrow. INTERVENTIONS: Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. LESSONS: High-dose systemic and intrathecal chemotherapy is safe and helpful for CCML extramedullary blast crisis. A long-term follow-up is crucial.
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Antineoplásicos/uso terapêutico , Crise Blástica/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Crise Blástica/complicações , Crise Blástica/tratamento farmacológico , Medula Óssea/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about their role in Non-small cell lung cancer (NSCLC). In the present study, we found that hsa_circ_0075930 expression levels were significantly higher in NSCLC cell lines and tissues. The elevated hsa_circ_0075930 expression was correlated with tumor size (Pâ¯=â¯0.001) and Lymph node metastasis (Pâ¯=â¯0.038). Functional experiments showed knockdown of hsa_circ_0075930 followed by RNA silencing restrained cell proliferation and induced cell cycle arrest of NSCLC cells. In addition, hsa_circ_0075930 suppression impaired migration and invasion potential by reversing epithelial-to-mesenchymal transition (EMT). These results indicated that hsa_circ_0075930 upregulation may be a critical oncogene and potential new biomarker in NSCLC.
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Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Pontos de Checagem do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Oncogenes , RNA Neoplásico , RNA não Traduzido , Células A549 , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Invasividade Neoplásica , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismoRESUMO
The cell cycle is a dynamic process with multiple phases regulating cell growth. The proper regulation is essential for avoiding errors and activation of cell death. Tumour suppressor proteins, including tuberin, are crucial in coordinating adequate cell growth and properly timed cell division. So, the present review article is focused on the latest aspects of the tuberin in the process of carcinogenesis. The PubMed was the main database used for the collection of latest data relating to multiple aspects of tuberin especially in context of cancer. Most of the recent studies revealed that mutation, truncation, and deregulation of the tuberin protein could definitely lead to cancer. Recent studies are also devoted to explore implications towards better understanding the progression of disease involving mis-regulated tuberin.
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Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young adult (20-39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Recent studies have revealed improvement in survival over time for all age groups and subtypes of leukaemia. However, these outcomes varied widely by age and are associated with sociodemographic and clinical factors. The present review concludes that survival and early death after acute leukaemia has greatly improved among young patients. However, inequalities in outcomes remain and are likely a result of multiple factors.
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Multidrug resistance (MDR) is the primary barrier to the success of chemotherapy for lung adenocarcinoma. MicroRNA (miR)-134, which is downregulated in lung adenocarcinoma, influences cell proliferation, apoptosis and invasion of lung adenocarcinoma. However, the function of miR-134 in the MDR of lung adenocarcinoma remains unclear. In the present study, it was identified that miR-134 expression is significantly downregulated in A549/cisplatin MDR lung adenocarcinoma cells, as compared with A549 parental cells. miR-134 regulates the sensitivity of lung adenocarcinoma cells to certain anticancer drugs. Furthermore, it was demonstrated that forkhead box M1 and multidrug resistance-associated protein 1 are functional targets of miR-134. These data revealed an important role for miR-134 in the regulation of MDR in lung adenocarcinoma.
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AIM: The aim of the study is to investigate the association of interferon gamma (IFN-γ) and interleukin-10 (IL-10) gene single nucleotide polymorphisms with the susceptibility of hemophagocytic lymphohistiocytosis (HLH) in Chinese children without known family history of HLH. PROCEDURE: Forty children with HLH and 160 age- and gender-matched healthy controls from Xuzhou Children's Hospital were enrolled in the study. Serum IFN-γ and IL-10 levels were measured by enzyme linked-immunosorbent assay. Polymorphisms of the IFN-γ gene at position +874 and +2109, and IL-10 at position -1082 were analyzed by allele-specific PCR. RESULT: Median serum concentrations of IFN -γ and IL-10 were significantly higher in children with HLH compared to healthy controls. The frequencies of IFN-γ +874 T/A and T/T genotypes, as well as T allele, were significantly higher in the HLH group compared with those in the control group. The frequencies of IL-10 -1082 G/A genotype and G allele were significantly increased in HLH patients compared with healthy controls. No significant difference was found in the distribution of IFN-γ +2109G/A genotypes between children with HLH and controls. CONCLUSION: This study presents preliminary evidence for the association between IFN +874 T/A, T/T, IL-10 -1082 A/G genotypes, and HLH susceptibility in Chinese children with HLH.
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Predisposição Genética para Doença/genética , Interferon gama/genética , Interleucina-10/genética , Linfo-Histiocitose Hemofagocítica/genética , Povo Asiático/genética , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Humanos , Lactente , Interferon gama/sangue , Interleucina-10/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To investigate the effect of phosphoinositide 4-phosphate (PI4P) on human glioma U87 cells and the mechanism of action of PI4P in the development of human glioma through the overexpression or silencing of PI4P in human glioma U87 cells, and to provide a new target for basic research and clinical treatment of glioma. METHODS: LV-Helper1, LV-Helper2, pWPXLd-PI4P, and pLL3.7-shPI4P were used to package pWPXLd-PI4P and pLL3.7-shPI4P lentiviruses. The U87-GFP (PI4P-overexpression control group), U87-GFP-PI4P (PI4P-overexpression experimental group), U87-Scramble (PI4P-silencing control group), and U87-shPI4P (PI4P-silencing experimental group) cell lines were established. Wound-healing assay and Transwell assay were used to evaluate cell migration and invasion, and Western blot was used to measure the expression of PI4P in each group. RESULTS: Western blot detected the expression of exogenous PI4P in the U87-GFP-PI4P cell line, and the U87-shPI4P cell line showed reduced expression of PI4P compared with the U87-Scramble cell line in the control group. The U87-GFP-PI4P cell line with PI4P overexpression had a significantly stronger ability of migration than the U87-GFP cell line in the control group (P<0.01); the U87-shPI4P cell line with PI4P silencing had a reduced ability of migration than the U87-Scramble cell line in the control group (P<0.01). The U87 cell line with PI4P overexpression had a significantly stronger invasion ability than the control group (P<0.05); after PI4P silencing, the experimental group showed a significant reduction in invasion ability compared with the control group (P<0.05). CONCLUSIONS: In human glioma U87 cells, PI4P can promote the invasion and migration of glioma cells and may become a new target in the basic research and clinical treatment of glioma.
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Glioma/patologia , Fosfatos de Fosfatidilinositol/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Invasividade NeoplásicaRESUMO
Cisplatin resistance is a major obstacle in the treatment of lung adenocarcinoma (LAD), and its mechanism has not been fully elucidated. Here, we report that miR-326 is downregulated in cisplatin-resistant A549/CDDP cells compared with parental A549 cells. Overexpression of miR-326 reversed cisplatin chemoresistance of LAD cells in vitro and in vivo. Moreover, we identified the specificity protein 1 (SP1) gene as a novel direct target of miR-326. Knockdown of SP1 revealed similar effects as that of ectopic miR-326 expression. Decreased miR-326 expression was also detected in tumor tissues sampled from LAD patients treated with cisplatin-based chemotherapy and was proved to be correlated with high expression of SP1 and decreased sensitivity to cisplatin. Furthermore, we show that the long noncoding RNA HOTAIR repression reverses chemoresistance of LAD cells partially through modulation of miR-326/SP1 pathway. In summary, we unveil a branch of the HOTAIR/miR-326/SP1 pathway that regulates chemoresistance of LAD cells.
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Adenocarcinoma/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Interferência de RNA , Fator de Transcrição Sp1/genética , Regiões 3' não Traduzidas , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Antineoplásicos/farmacologia , Sequência de Bases , Linhagem Celular Tumoral , Cisplatino/farmacologia , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genéticaRESUMO
Accumulating evidence indicates that the lncRNAs play a critical role in cancer progression and metastasis. In this study, we found that MALAT1 upregulation was associated with larger tumor size and lymph-node metastasis, and also correlated with shorter overall survival of lung adenocarcinoma patients. Furthermore, MALAT1 promotes EMT and metastasis of lung adenocarcinoma cells in vitro and in vivo. In particular, MALAT1 upregulated the expression of miR-204 target gene SLUG through competitively 'spongeing' miR-204. In summary we unveil a branch of the MALAT1/miR-204/SLUG pathway that regulates the progression of lung adenocarcinoma.