Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.
BMC Cancer
; 24(1): 79, 2024 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-38225540
ABSTRACT
BACKGROUND:
GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS.METHODS:
GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments.RESULTS:
The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression.CONCLUSION:
Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Rabdomiosarcoma
/
MicroARNs
/
Serina-Treonina Quinasas TOR
/
ARN Largo no Codificante
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Cancer
/
BMC cancer
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China