YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer

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	YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer
	Jiang, DW; Qiu, T; Peng, JJ; Li, SY; Tala; Ren, WL; Yang, CY; Wen, Y; Chen, CH; Sun, J; Wu, YY; Liu, R; Zhou, J; Wu, KM; Liu, W; Mao, XY; Zhou, ZM; Chen, CS
	2022
发表期刊	CELL DEATH AND DIFFERENTIATION
ISSN	1350-9047
卷号	29 期号:6 页码:1283-1295
摘要	Y-box binding protein 1 (YB-1) is a well-known oncogene highly expressed in various cancers, including basal-like breast cancer (BLBC). Beyond its role as a transcription factor, YB-1 is newly defined as an epigenetic regulator involving RNA 5-methylcytosine. However, its specific targets and pro-cancer functions are poorly defined. Here, based on clinical database, we demonstrate a positive correlation between Kruppel-like factor 5 (KLF5) and YB-1 expression in breast cancer patients, but a negative correlation with that of Dachshund homolog 1 (DACH1). Mechanistically, YB-1 enhances KLF5 expression not only through transcriptional activation that can be inhibited by DACH1, but also by stabilizing KLF5 mRNA in a RNA 5-methylcytosine modification-dependent manner. Additionally, ribosomal S6 kinase 2 (RSK2) mediated YB-1 phosphorylation at Ser102 promotes YB-1/KLF5 transcriptional complex formation, which co-regulates the expression of BLBC specific genes, Keratin 16 (KRT16) and lymphocyte antigen 6 family member D (Ly6D), to promote cancer cell proliferation. The RSK inhibitor, LJH685, suppressed BLBC cell tumourigenesis in vivo by disturbing YB-1-KLF5 axis. Our data suggest that YB-1 positively regulates KLF5 at multiple levels to promote BLBC progression. The novel RSK2-YB-1-KLF5-KRT16/Ly6D axis provides candidate diagnostic markers and therapeutic targets for BLBC.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13670
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Jiang, DW,Qiu, T,Peng, JJ,et al. YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer[J]. CELL DEATH AND DIFFERENTIATION,2022,29(6):1283-1295.
APA	Jiang, DW.,Qiu, T.,Peng, JJ.,Li, SY.,Tala.,...&Chen, CS.(2022).YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer.CELL DEATH AND DIFFERENTIATION,29(6),1283-1295.
MLA	Jiang, DW,et al."YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer".CELL DEATH AND DIFFERENTIATION 29.6(2022):1283-1295.

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2023032910.pdf（8764KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文