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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."xsd:string
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http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/author"Fang Z."xsd:string
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http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/author"Shao N."xsd:string
http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/name"Mol Biol Rep"xsd:string
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http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/title"DLGAP1-AS2 promotes estrogen receptor signalling and confers tamoxifen resistance in breast cancer."xsd:string
http://purl.uniprot.org/citations/35449318http://purl.uniprot.org/core/volume"49"xsd:string
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