YTHDF1/RNF7/p27 axis promotes prostate cancer progression

	YTHDF1/RNF7/p27 axis promotes prostate cancer progression
	Shi, YL; Liu, BY; Zhang, Y; Zhao, S; Zuo, L; Pu, J; Zhai, HQ; Mu, DC; Du, J; Cheng, Y; Yang, CP; Chen, YB
	2025
发表期刊	Cell Death Dis.
ISSN	2041-4889
卷号	16 期号:1
摘要	Prostate cancer (PCa) is a prevalent malignant tumor of the urinary system and remains the most common cancer among males. In this study, we showed that YTHDF1, one of the reader proteins involved in the N6-methyladenosine (m6A) modification signaling pathway, is highly expressed in PCa cancerous tissues and cells, which correlates with poor clinical outcomes. Our study revealed that YTHDF1 knockdown inhibits tumor cell proliferation, migration, and xenograft tumor formation by decreasing p27 protein stability through proteasome degradation signaling. Consistently, YTHDF1 depletion markedly reduced the clonogenic growth of Pten or/and TP53-deficient organoids. Candidate p27-targeting E3 ubiquitin ligases screening identified RNF7 as the direct downstream target for YTHDF1 in an m6A-dependent manner. The subsequent high translation of RNF7 results in the efficient degradation of the cell cycle inhibitor p27 and malignant tumor cell growth. In addition, we provided evidence showing that YTHDF1 or RNF7 depletion sensitizes tumor cells to chemotherapy drug cisplatin by increasing cellular apoptosis. Our findings revealed that the neddylation inhibitor MLN4924 effectively inhibited prostate cancer progression in vitro and in vivo. Our study highlights the YTHDF1/RNF7/p27 axis as a crucial component in PCa, suggesting its potential as a novel therapeutic target.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14906
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Shi, YL,Liu, BY,Zhang, Y,et al. YTHDF1/RNF7/p27 axis promotes prostate cancer progression[J]. Cell Death Dis.,2025,16(1).
APA	Shi, YL.,Liu, BY.,Zhang, Y.,Zhao, S.,Zuo, L.,...&Chen, YB.(2025).YTHDF1/RNF7/p27 axis promotes prostate cancer progression.Cell Death Dis.,16(1).
MLA	Shi, YL,et al."YTHDF1/RNF7/p27 axis promotes prostate cancer progression".Cell Death Dis. 16.1(2025).

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