Long non-coding RNA terminal differentiation-induced non-coding RNA regulates cisplatin resistance of choroidal melanoma by positively modulating extracellular signal-regulated kinase 2 via sponging microRNA-19b-3p.
Bioengineered
; 13(2): 3422-3433, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-35067169
ABSTRACT
In the present study, we aimed to investigate the role of long non-coding RNA terminal differentiation-induced non-coding RNA (TINCR) in cisplatin (DDP) resistance of choroidal melanoma (CM) and the potential molecular mechanisms. CM and non-CM tissues were collected from 60 CM patients. DDP-resistant CM cells were obtained by selection with linearly increased DDP treatment. The expression levels of TINCR, microR-19b-3p (miR-19b-3p), and extracellular signal-regulated kinase 2 (ERK-2) were detected by quantitative real-time PCR. Cholecystokinin octapeptide (CCK-8) assay was utilized to detect chemosensitivity and cell viability. Flow cytometry analysis was performed to detect apoptotic cells. The protein levels of Bax, Bcl-2, cleaved-caspase-3, ERK-2, and nuclear factor-kappa B p65 were measured by Western blot. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to determine the relationship among TINCR, miR-19b-3p, and ERK-2. The results showed that the levels of TINCR and ERK-2 were markedly increased in DDP-resistant CM tissues and cells, while miR-19b-3p level was significantly reduced. TINCR knockdown reduced DDP resistance and cell viability and promoted cell apoptosis, while TINCR overexpression exhibited opposite effects. TINCR and ERK-2 were direct targets of miR-19b-3p. Further experiments revealed that TINCR enhanced DDP resistance in CM cells by regulating the miR-19b-3p/ERK-2/NF-kb axis. Taken together, our study revealed a critical role of TINCR in regulating DDP resistance in CM and suggested that TINCR is a potential cisplatin-resistant CM therapeutic target.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Neoplásico
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Neoplasias da Coroide
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Cisplatino
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Resistencia a Medicamentos Antineoplásicos
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Proteína Quinase 1 Ativada por Mitógeno
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Sistema de Sinalização das MAP Quinases
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MicroRNAs
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RNA Longo não Codificante
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Melanoma
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Bioengineered
Ano de publicação:
2022
Tipo de documento:
Article