Enhanced expression of lncRNA ZXF1 promotes cisplatin resistance in lung cancer cell via MAPK axis.
Exp Mol Pathol
; 116: 104484, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32533982
ABSTRACT
Long non-coding RNA (lncRNA) ZXF1 has recently been associated with the poor prognosis of lung cancer by promoting metastasis. However, little is known regarding the role of ZXF1 in lung cancer treatment and the underlying mechanism. Here, using lung cancer tissue and chemoresistant lung cancer cells, we investigated the interaction of ZXF1 with the efficacy of cisplatin, the first-line chemotherapy for lung cancer. We found that ZXF1 overexpression in lung cancer tissue increased the risk of treatment failure and tumor recurrence. We also provided evidence that ZXF1 contributed to cisplatin resistance and cancer progression via activating ERK, JNK and p38-mediated MAPK signaling cascade. In contrast, deactivating MAPK pathway by ZXF1 silencing enhanced cisplatin-induced cell cycle arrest and apoptosis by activating p53/p21 axis. Moreover, ZXF1 knockdown suppressed MAPK-regulated expression of MMP-2 and MMP-9, the enzymes responsible for degrading extracellular matrix, and thus decreased the invasion and migration capability of the cells. All these changes inhibited rapid cell proliferation and restored cellular sensitivity to cisplatin treatment. Taken together, our study revealed that lncRNA ZXF1 contributes to cisplatin resistance and leads to the poor prognosis of lung cancer via activating MAPK pathway, which represents as a promising target to optimize lung cancer treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_other_respiratory_diseases
/
6_trachea_bronchus_lung_cancer
Asunto principal:
Cisplatino
/
Resistencia a Antineoplásicos
/
ARN Largo no Codificante
/
Neoplasias Pulmonares
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Exp Mol Pathol
Año:
2020
Tipo del documento:
Article
País de afiliación:
China