RESUMO
Glioblastoma (GBM) has been regarded as the most aggressive disease in the nervous system. Accumulating literatures have illustrated the crucial role of competing endogenous RNAs (ceRNAs) network in the pathogenesis and progression of various tumors. The promoting effect of LEF1-AS1 on GBM development has been previously identified. This study attempted to explore the underlying mechanism of LEF1-AS1 in GBM. Data of clinical GBM patients was downloaded from TCGA and GEO databases. The proliferative ability, clonogenic vitality, invasive, and migratory capabilities of GBM cells were measured using Cell counting kit-8 (CCK-8), colony formation and transwell assays. Luciferase reporter gene analysis was performed to verify the correlations between LEF1-AS1/EN2 and miR-543. qRT-PCR and western blotting were implemented to evaluate the mRNA and protein levels, respectively. Our results consolidated that LEF1-AS1 was highly expressed in GBM tissue specimens and its up-regulation induced unfavorable prognosis. The loss/gain-of-function analyses verified that LEF1-AS1 promoted the GBM cell malignant behaviors. Mechanically, LEF1-AS1 acted as a ceRNA for miR-543 and positively regulated engrailed homeobox 2 (EN2) expression. Down-regulation of miR-543 elevated GBM cell malignant behaviors, which was reversed by LEF1-AS1 knockdown. Meanwhile, the LEF1-AS1 inhibition could arrest the promoting effect of high-regulated EN2 on GBM cell aggressiveness and vice versa. In conclusion, our findings identified LEF1-AS1 as a ceRNA for miR-543 and showed that EN2 was positively regulated by LEF1-AS1. The LEF1-AS1/miR-543/EN2, as a novel ceRNA network, was implicated in the progression of GBM, which provided a novel insight for GBM treatment.
Assuntos
Glioblastoma/genética , Fator 1 de Ligação ao Facilitador Linfoide/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Bases de Dados Genéticas , Progressão da Doença , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética , Transcriptoma/genéticaRESUMO
OBJECTIVE: To elucidate the therapeutic effect of subtemporal decompressive craniotomy with large flap resection on serious craniocerebral injury associated with cerebral infarction. METHODS: Forty-eight cases of serious head injury accompanied by cerebral infarction were classified into two groups with each having 24 cases: treatment group, in which large bone-flap decompressive craniotomy was performed; control group, in which routine craniotomy and hematoma evacuation were adopted. The status of cerebral infarction pre- and post-operation, as well as the curative effect 3 months after operation were comparatively analysed between the two groups. RESULTS: There was no significant difference regarding the status of cerebral infarction on the first day after operation; while one week after operation, the size of cerebral infarction was significantly smaller in treatment group than control one (P less than 0.05). Postoperative 3 months, the mortality rate was 20.8% in treatment group, being evidently superior to that of control group (33.3%, P less than 0.05). The mo- derate disability (good and fair) rate was 41.7% in treatment group, significantly higher than that in control group (25.0%, P less than 0.05). CONCLUSION: Large bone-flap decompressive craniotomy is confirmed effective and hence it offers us a preferable alternative of treatment by which to reduce disability and fatality rates for patients with serious head injury accompanied by cerebral infarction.
