Suppression of LncRNA AC008406.3 sensitizes breast cancer cells to docetaxel via triggering cuproptosis

Background: Docetaxel (DTX) is one of the commonly used chemotherapeutic agents for breast Cancer. Cuproptosis, a newly defined form of cell death, significantly influences tumor progression. This study aims to identify cuproptosis-related long non-coding RNAs (lncRNAs) involved in regulating the sensitivity of breast Cancer to DTX.

Materials: Cuproptosis-related prognostic lncRNAs in breast Cancer were identified through integrated co-expression, differential expression, and prognostic analyses based on the TCGA-BRCA cohort. The role of the identified lncRNA AC008406.3 in regulating Cuproptosis in breast Cancer cells was experimentally verified. The impact of DTX on the induction of Cuproptosis was investigated, and rescue experiments were conducted to validate the involvement of AC008406.3 in modulating breast Cancer sensitivity to DTX.

Results: AC008406.3 was identified as a potential cuproptosis-related prognostic lncRNA in breast Cancer, exhibiting high expression in breast Cancer samples, which was associated with unfavorable prognostic outcomes. Knockdown of AC008406.3 specifically induced Cuproptosis in breast Cancer cells, as evidenced by increased intracellular copper levels and downregulation of lipoylated proteins and Fe-S cluster proteins, thereby suppressing cell proliferation, invasion, and migration; conversely, AC008406.3 overexpression elicited opposite phenotypic changes. Notably, DTX induced the occurrence of Cuproptosis in breast Cancer, whereas AC008406.3 suppressed this process, thereby diminishing DTX efficacy. However, AC008406.3 knockdown synergistically enhanced the anti-tumor efficacy of DTX in inhibiting breast Cancer growth.

Conclusion: AC008406.3 reduces the sensitivity of breast Cancer to DTX by suppressing Cuproptosis. Targeting AC008406.3 may represent a potential strategy to sensitize breast Cancer cells to DTX.