LINC02207 suppresses breast cancer progression by promoting cuproptosis through NFAT5 regulation.

Background

Breast cancer remains a leading cause of cancer-related mortality worldwide, with triple-negative breast cancer (TNBC) representing a particularly aggressive subtype lacking targeted therapies. Inducing copper-mediated cell death stands as a significant therapeutic approach for tumors; however, research into non-coding RNA regulation of copper-mediated cell death in TNBC remains relatively scarce. This study analyses transcriptomic data from TNBC patients to identify long non-coding RNAs (lncRNAs) associated with copper-mediated cell death, aiming to uncover potential therapeutic targets.

Methods

Bioinformatics analysis of transcriptomic data from breast cancer patients in the TCGA databases identified a key gene associated with copper-mediated cell death. The role of this gene in breast cancer tumor growth was then investigated at molecular, cellular, and animal model levels. RESULT This study finds long non-coding RNA LINC02207 is significantly downregulated in TNBC tissues and low expression correlates with poorer survival. It localizes in nucleus, acts as tumor suppressor by inhibiting cell proliferation, positively regulates cuproptosis and enhances sensitivity to Elesclomol. Knockdown impairs cuproptosis by modulating key genes. Mechanistically, NFAT5 is its nuclear binding partner. LINC02207 may regulate copper-dependent apoptosis by influencing the nuclear localisation of NFAT5, thereby influencing cancer progression. In vivo models confirm its overexpression suppresses tumor growth by promoting cuproptosis.

Conclusion

These findings reveal a critical tumor-suppressive role of LINC02207 mediated through NFAT5-dependent regulation of cuproptosis and suggest that LINC02207 may serve as a promising therapeutic target in breast cancer.