(485.1) DANCR acetylated-KLF5 induces cisplatin resistance in triple-negative breast cancer by inhibiting the transcription of p27Kip1

Poster Board Number: A28

Jianming Tang (The First Hospital of Lanzhou University, The First Hospital of Lanzhou University)

Cisplatin is used as a common chemotherapy drug in triple-negative breast cancer. However, although growing evidence demonstrates that its chemoresistance becomes a important obstacle for curing of triple-negative breast cancer, its molecular mechanism remains unclear. Here we detected that Krüppel-like factor 5 (KLF5) depletion reduce cisplatin chemoresistance both in triple-negative breast cancer cells in vitro and in vivo. Further experiments showed that long non-coding RNA DANCR binds with KLF5 and then induces the acetylation of KLF5 at lysine 369 (K369), which upregulates KLF5 protein level, contributing to cisplatin chemoresistant. Additionally,  DANCR/KLF5 signalling pathway renders chemoresistant hypersensitive to cisplatin that inhibiting p27 transcription. Our study uncover a novel DANCR/KLF5/p27 signalling pathway to mediate cisplatin chemoresistant in triple-negative breast cancer and provide a new molecular target for treatment of triple-negative breast cancer.

Zhejiang Provincial Nature Science Foundation of China (Grant number: LQ20H160063 to Jianming Tang), Gansu Provincial National Science Foundation for Distinguished Young Scholars (Grant number: 21JR7RA389 to Jianming Tang).



Co-expression of DANCR, KLF5, and p27 clinical triple-negative breast cancer samples.