TMED2 Induces Cisplatin Resistance in Breast Cancer via Targeting the KEAP1-Nrf2 Pathway.
Curr Med Sci
; 43(5): 1023-1032, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37615927
ABSTRACT
OBJECTIVE:
Cisplatin is the first-line treatment for breast cancer, but it faces challenges of drug resistance. This study investigated new molecular mechanisms underlying cisplatin resistance in breast cancer.METHODS:
We analyzed sequencing data from the TCGA database to identify potential associations between transmembrane emp24 protein transport domain containing 2 (TMED2) and breast cancer. Western blotting, real-time PCR, CCK-8, and TUNEL assays were used to measure the effects and molecular mechanism of TMED2 on cisplatin resistance in MCF-7 and MDA-MB-231 cell lines.RESULTS:
TMED2 was overexpressed in breast cancer and associated with poor prognosis. TMED2 increased cisplatin resistance in breast cancer cells in vitro via promoting ubiquitination of Kelch-like ECH-associated protein 1 (KEAP1), relieving inhibition of KEAP1 on nuclear factor erythroid 2-related factor 2 (Nrf2), and increasing expression of downstream drug resistance related genes, such as heme oxygenase 1 (HO-1) and NAD (P) H quinone oxidoreductase 1 (NQO1).CONCLUSION:
We identified a new molecular mechanism by which TMED2 affects cisplatin resistance in breast cancer. Our results provide theoretical guidance for future clinical applications.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Cisplatino
/
Resistencia a Medicamentos Antineoplásicos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Curr Med Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China