RESUMO
Abnormal methylation genes usually act as oncogenes or anti-oncogenes in the occurrence and development of tumor, indicating their potential role as biomarkers in the evaluation of malignant tumor. However, the research on methylation's association with glioblastoma was rare. We attempted to figure out whether the methylation of genes could serve as the biomarker in evaluating the malignant degree of GBM. Methylation microarray data of 275 GBM patients have been downloaded from The Cancer Genome Atlas (TCGA) dataset. Logistic regression was used to find the methylated genes associated with the malignant degree of patients with the tumor. Functional enrichment analysis and network analysis were further performed on these selected genes. A total of 668, 412, 470, and 620 genes relevant with the methylation or demethylation were found to be associated with the malignant degree, Grades 1-4 of tumor. The higher the degree of malignant tumor, the higher of its methylation degree of its corresponding genes. GO and KEGG analysis results showed that these methylated genes were enriched in many functions as cell adhesion, abnormal transcription, and cell cycle disorder, etc. Of note, CCL11 and LCN11 were found to be significantly related to the progression of GBM. Critical genes associated with cell cycle as CCL11 and LCN1 may play essential roles in the occurrence, development, and transition of glioblastoma. More research was needed to explore its potential molecular mechanism.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Metilação de DNA , Glioblastoma/genética , Neoplasias Encefálicas/patologia , Quimiocina CCL11/genética , Distribuição de Qui-Quadrado , Biologia Computacional , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioblastoma/patologia , Humanos , Lipocalinas/genética , Modelos Logísticos , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência com Séries de OligonucleotídeosRESUMO
The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area.
Assuntos
Sistemas CRISPR-Cas , Neoplasias/genética , Neoplasias/metabolismo , Animais , Epigênese Genética , Humanos , Mutação , Neoplasias/terapia , Edição de RNA , RNA Guia de Cinetoplastídeos/genéticaRESUMO
Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be responsible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.
