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DANCR acetylated‐KLF5 induces cisplatin resistance in triple‐negative breast cancer by inhibiting the transcription of p27 Kip1
Author(s) -
Tang Jianming
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r3018
Subject(s) - triple negative breast cancer , cisplatin , breast cancer , cancer research , acetylation , transcription factor , cancer , biology , chemistry , medicine , chemotherapy , gene , biochemistry
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.