DLGAP1-AS2 promotes estrogen receptor signalling and confers tamoxifen resistance in breast cancer.
Mol Biol Rep
; 49(5): 3939-3947, 2022 May.
Article
en En
| MEDLINE
| ID: mdl-35449318
ABSTRACT
BACKGROUND:
Tamoxifen is a first-line endocrine agent and is often used to treat estrogen receptor-positive (ER+) breast cancer. Unfortunately, approximately 30-40% of patients who received tamoxifen therapy experience recurrence or progression to a fatal advanced stage due to tamoxifen resistance. However, the mechanisms of tamoxifen resistance remain unclear.METHODS:
The expression of lncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) was detected by qPCR. The effect of DLGAP1-AS2 on tamoxifen resistance was evaluated by MTT, colony formation, TUNEL and flow cytometric assays. The mechanisms by which DLGAP1-AS2 regulates tamoxifen resistance were investigated through qPCR, RNA pull-down assays and RNA immunoprecipitation (RIP) assays.RESULTS:
Our results showed that DLGAP1-AS2 is significantly upregulated in breast cancer and that tamoxifen can induce DLGAP1-AS2 expression. Further investigation suggested that upregulation of DLGAP1-AS2 can increase cell viability and inhibit apoptosis, while downregulation of DLGAP1-AS2 results in the opposite effects. Mechanistically, DLGAP1-AS2 can bind to the AFF3 protein to inhibit its degradation, which further promotes ER signalling.CONCLUSIONS:
Our research clarified that DLGAP1-AS2 promotes ER signalling to induce tamoxifen resistance and that targeting DLGAP1-AS2 might be a promising strategy to overcome tamoxifen resistance in breast cancer.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Tamoxifeno
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Neoplasias de la Mama
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Resistencia a Antineoplásicos
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ARN Largo no Codificante
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Proteínas Asociadas a SAP90-PSD95
Límite:
Female
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Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article