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1.
Metab Brain Dis ; 38(5): 1531-1542, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36867300

RESUMO

Increasing number of studies have proven that circular RNAs (circRNAs) play a major role in the biological processes of many different cancers, including glioma, especially as competitive molecular sponges of microRNAs (miRNAs). However, the clear molecular mechanism of the circRNA network in glioma is still not well understood. The expression level of circRNA-104718 and microRNA (miR)-218-5p in glioma tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target protein's expression level was assessed by western blotting. Bioinformatics systems were used to predict the possible microRNAs and target genes of circRNA-104718, after which dual-luciferase reporter assays were used to confirm the predicted interactions. The proliferation, invasion, migration and apoptosis of glioma cells were detected by CCK, EdU, transwell, wound-healing and flow cytometry assays. CircRNA-104718 was upregulated in human glioma tissues, and a higher level of circRNA-104718 indicated poorer outcomes in glioma patients. In contrast, in glioma tissues, miR-218-5p was downregulated. Knockdown of circRNA-104718 suppressed migration and invasion while boosting the apoptosis rate of glioma cells. In addition, the upregulation of miR-218-5p in glioma cells caused the same suppression. Mechanistically, circRNA-104718 inhibited the protein expression level of high mobility group box-1 (HMGB1) by acting as a molecular sponge for miR-218-5p. CircRNA-104718 is a suppressive factor in glioma cells and might represent a new target for the treatment of glioma patients. CircRNA-104718 modulates glioma cell proliferation through the miR-218-5p/HMGB1 signalling axis. CircRNA-104718 provides a possible mechanism for understanding the pathogenesis of glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Proteína HMGB1 , MicroRNAs , Transdução de Sinais , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Glioma/genética , Glioma/patologia , Proteína HMGB1/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
2.
Mol Carcinog ; 61(6): 558-571, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35384084

RESUMO

Glioma is the most common primary malignant intracranial tumor in humans, and glioblastoma (GBM) has been associated with a more aggressive histology and poorer prognosis. There is growing evidence that circular RNAs (circRNAs) are involved in the progression of various malignancies; however, the role and molecular mechanism of circRNAs in glioma remain elusive. In the present study, we screened for differentially expressed circRNAs in gliomas by using a bioinformatics method. Significant upregulation in glioma tissues was verified by quantitative real-time polymerase chain reaction (qRT-PCR), and the prognostic value was evaluated. The potential oncogenic role of circular RNA TCF25 (circTCF25) in glioma was assessed both in vivo and in vitro. Bioinformatics analysis and luciferase reporter assays confirmed the interaction among circTCF25, microRNA-206 (miR-206), and its target gene Cyclophilin B (CypB). circTCF25 was predominantly located in the cytoplasm; the combination of mir-206 and circTCF25 reverses the effects of knockdown of circTCF25 on the proliferation, migration, invasion, and tumorigenesis of glioma cells. Competitive binding between circTCF25 and miR-206 mainly upregulates target gene CypB expression by preventing its inhibition of the Jak2/p-stat3 pathway. In addition, knockdown of circTCF25 reduced CypB expression by inhibiting JAK2/p-stat3, which was rescued by treatment with a miR-206 inhibitor. In summary, our findings demonstrate that the circTCF25/miR-206/CypB axis plays a vital role in glioma progression, migration, invasion, and tumorigenesis.


Assuntos
Glioma , MicroRNAs , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclofilinas , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
3.
Adv Sci (Weinh) ; 9(30): e2202149, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36039936

RESUMO

The execution of biological activities inside space-limited cell nuclei requires sophisticated organization. Current studies on the 3D genome focus on chromatin interactions and local structures, e.g., topologically associating domains (TADs). In this study, two global physical properties: DNA density and distance to nuclear periphery (DisTP), are introduced and a 2D matrix, D2 plot, is constructed for mapping genetic and epigenetic markers. Distinct patterns of functional markers on the D2 plot, indicating its ability to compartmentalize functional genome regions, are observed. Furthermore, enrichments of transcription-related markers are concatenated into a cross-species transcriptional activation model, where the nucleus is divided into four areas: active, intermediate, repress and histone, and repress and repeat. Based on the trajectories of the genomic regions on D2 plot, the constantly active and newly activated genes are successfully identified during olfactory sensory neuron maturation. The analysis reveals that the D2 plot effectively categorizes functional regions and provides a universal and transcription-related measurement for the 3D genome.


Assuntos
Cromatina , Histonas , Histonas/genética , Cromatina/genética , Genoma/genética , DNA/genética , Genômica
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