The KLF16/MYC feedback loop is a therapeutic target in bladder cancer

作者：Lisi Zheng, Jingxuan Wang, Shan Han, Li Zhong, Zefu Liu, Bin Li, Ruhua Zhang, Liwen Zhou, X.F. Steven Zheng, Zhenhua Liu, Cuiling Zeng, R Li, Yezi Zou, Liqin Wang, Yuanzhong Wu, Tiebang Kang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-024-03224-3 · 被引用次数：9 · 研究领域：Kruppel-like factors research、Coagulation, Bradykinin, Polyphosphates, and Angioedema、Genetic and Kidney Cyst Diseases

BACKGROUND: Bladder cancer (BLCA) is a common malignancy characterized by dysregulated transcription and a lack of effective therapeutic targets. In this study, we aimed to identify and evaluate novel targets with clinical potential essential for tumor growth in BLCA. METHODS: CRISPR-Cas9 screening was used to identify transcription factors essential for bladder cancer cell viability. The biological functions of KLF16 in bladder cancer were investigated both in vitro and in vivo. The regulatory mechanism between KLF16 and MYC was elucidated through a series of analyses, including RNA sequencing, quantitative polymerase chain reaction (qPCR), RNA immunoprecipitation, Western blotting, Mass spectrometry, Dual-luciferase reporter assays, Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, OptoDroplets assays, and RNA stability assay. The clinical relevance of KLF16 and MYC in bladder cancer was evaluated through analyses of public databases and immunohistochemistry. RESULTS: Krüppel-like factor 16 (KLF16) was essential for BLCA cell viability. Elevated expression of KLF16 was observed in bladder cancer tissues, and higher expression levels of KLF16 were correlated with poor progression-free survival (PFS) and cancer-specific survival (CSS) probabilities in BLCA patients. Mechanistically, KLF16 mRNA competed with the mRNA of dual-specificity phosphatase 16 (DUSP16) for binding to the RNA-binding protein, WW domain binding protein 11 (WBP11), resulting in destabilization...