RESUMO
PURPOSE: Autophagy plays a critical role in PCa development. DAXX has a potent pro-survival effect by enhancing cell growth in PCa via suppression of autophagy. Here, we depicted a network governed by DAXX and SPOP by which the autophagy pathway is suppressed through the ubiquitination and modulation of key cellular signaling pathways mediators including LAMP2 and RARRES1. MATERIALS AND METHODS: Through network-based bioinformatics approaches, the expression levels of DAXX, RARRES1, LAMP2, and SPOP genes was assessed in 50 PCa tissues and 50 normal adjacent from the same sample as well as 50 benign prostatic hyperplasia (BPH) tissues by quantitative RT-PCR. The normal adjacent tissues were taken from regions more than 5mm away from the bulk of those tumor tissues with clearly distinct margins. RNA extraction, cDNA synthesis and Real-time Quantitative RT-PCR were done for assessment of gene expression. To evaluate the primary gene network centered on autophagy pathway, according to the Query-dependent weighting algorithm, these two networks were integrated with Cytoscape 3.4 software. RESULTS: We found that in PCa tissues the DAXX expression level was significantly increased (P < 0.001) and the expressions of SPOP, RARRES1, and LAMP2 were significantly down-regulated, when compared to both control groups including normal adjacent and BPH tissues. Moreover, significant correlations were observed between expression levels of all four genes. Additionally, ROC curve analysis revealed that LAMP2 had the most sensitivity and specificity. CONCLUSION: These findings suggest that the contribution of SPOP, DAXX, RARRES1, and LAMP2 together could be a putative regulatory element acting as a prognostic signature and therapeutic target in PCa.
Assuntos
Autofagia/fisiologia , Proteínas Correpressoras/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteínas de Membrana/genética , Chaperonas Moleculares/genética , Proteínas Nucleares/genética , Hiperplasia Prostática , Neoplasias da Próstata , Proteínas Repressoras/genética , Biologia Computacional/métodos , Correlação de Dados , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Prognóstico , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismoRESUMO
PURPOSE: This study aims to investigate the expression level of mir-let7b-3p and mir-548, which are involved in PTEN expression in tissue samples of prostate cancer patients versus benign prostate hyperplasia (BPH) and normal adjacent tissue. MATERIALS AND METHODS: Prostate cancer tissues were obtained from patients after receiving informed consent. Total RNA extraction and cDNA synthesis were performed for determining gene expression. RESULTS: Ten patients were determined to have high Gleason scores (> 7), 36 and seven samples had intermediate Gleason scores (7?) and BPH, respectively, and 40 samples were derived from normal adjacent tissue. Downreg-ulation of mir-let7b and upregulation of mir-548 expression significantly correlated with high-risk Gleason scores. CONCLUSION: The present study showed that miR-let7b and/or mir-548 can be considered as potential targets in prostate cancer therapy.
Assuntos
MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologiaRESUMO
Osteoporosis is the most common multifactorial metabolic bone disorder worldwide with a strong genetic component. In this review, the evidence for a genetic contribution to osteoporosis and related phenotypes is summarized alongside with methods used to identify osteoporosis susceptibility genes. The key biological pathways involved in the skeleton and bone development are discussed with a particular focus on master genes clustered in these pathways and their mode of action. Furthermore, the most studied single nucleotide polymorphisms (SNPs) analyzed for their importance as genetic markers of the disease are presented. New data generated by next-generation sequencing in conjunction with extensive meta-analyses should contribute to a better understanding of the genetic basis of osteoporosis and related phenotype variability. These data could be ultimately used for identifying at-risk patients for disease prevention by both controlling environmental factors and providing possible therapeutic targets.
Assuntos
Osteoporose/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Osteogênese , Osteoporose/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genéticaRESUMO
Ameloblastic carcinoma (AC) is a rare malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Epidemiological evidence shows that human cancer is generally caused by genotoxic factors, genes involved in the susceptibility of cancer, including those involved in metabolism or detoxification of genotoxic environment and those controlling DNA replication. Nowadays, gene polymorphism has an important role in development of malignant tumor. We report a case series study of ameloblastic carcinoma and ameloblastoma to show the role of PKM2 and MAPK8IP2 polymorphisms in these tumors. The DNA was extracted separately from specimens in paraffin sections of the tumor. Polymorphism of these genes was determined by PCR-RFLP (Polymerase Chain Reaction-Restriction fragment length polymorphism) method. The allele distributions of all samples were in Hardy-Weinberg equilibrium. The genotype and allele distribution in these genes were not statistically different between patients and controls.