DANCR Induces Cisplatin Resistance of Triple-Negative Breast Cancer by KLF5/p27 Signaling

An increasing body of evidence suggests that long noncoding RNAs play critical roles in human cancer. Breast cancer is a heterogeneous disease and the potential involvement of long noncoding RNAs in breast cancer remains poorly understood. Herein, the study identified a long noncoding RNA, DANCR, which promotes cisplatin chemoresistance in triple-negative breast cancer (TNBC) cells. Mechanistically, binding of DANCR to Kruppel-like factor 5 (KLF5) induced acetylation of KLF5 at lysine 369 (K369), and DANCR knockdown resulted in down-regulation of KLF5 protein levels. Furthermore, DANCR/KLF5 signaling pathway induced hypersensitivity to cisplatin in chemoresistant patients by inhibiting p27 transcription. In summary, this study reinforced the potential presence of a growth regulatory network in TNBC cells, and documented a DANCR/KLF5/p27 signaling pathway mediating cisplatin chemoresistance in TNBC. (Am J Pathol 2023, 193: 248e258; https://doi.org/10.1016/j.ajpath.2022.11.007)

Automated summary

A study identified DANCR, a long noncoding RNA, as a promoter of cisplatin chemoresistance in triple-negative breast cancer cells. It was found that DANCR binds to KLF5 and induces acetylation of KLF5, resulting in down-regulation of KLF5 and hypersensitivity to cisplatin through the DANCR/KLF5/p27 signaling pathway.