例如:"lncRNA", "apoptosis", "WRKY"

PHF5A Epigenetically Inhibits Apoptosis to Promote Breast Cancer Progression.

Cancer Res.2018 Jun 15;78(12):3190-3206. Epub 2018 Apr 26
Yi-Zi Zheng 1 , Meng-Zhu Xue 2 , Hong-Jie Shen 3 , Xiao-Guang Li 4 , Ding Ma 1 , Yue Gong 1 , Yi-Rong Liu 1 , Feng Qiao 4 , Hong-Yan Xie 1 , Bi Lian 1 , Wei-Li Sun 4 , Hai-Yun Zhao 1 , Ling Yao 4 , Wen-Jia Zuo 1 , Da-Qiang Li 4 , Peng Wang 5 , Xin Hu 1 , Zhi-Ming Shao 1
Yi-Zi Zheng 1 , Meng-Zhu Xue 2 , Hong-Jie Shen 3 , Xiao-Guang Li 4 , Ding Ma 1 , Yue Gong 1 , Yi-Rong Liu 1 , Feng Qiao 4 , Hong-Yan Xie 1 , Bi Lian 1 , Wei-Li Sun 4 , Hai-Yun Zhao 1 , Ling Yao 4 , Wen-Jia Zuo 1 , Da-Qiang Li 4 , Peng Wang 5 , Xin Hu 1 , Zhi-Ming Shao 1
+ et al

[No authors listed]

Author information
  • 1 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 2 SARI center for Stem Cell and Nanomedicine, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
  • 3 Epigenetics Laboratory, Institutes of Biomedical Sciences and School of Basic Medicine, Shanghai Medical College of Fudan University, Shanghai, China.
  • 4 Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • 5 Bio-Med Big Data Center, Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

摘要


Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in breast cancer development have not yet been elucidated. Using an in vivo CRISPR screen targeting RNA-binding proteins, we identified PHD finger protein 5A (PHF5A) as a key splicing factor involved in tumor progression. PHF5A expression was frequently upregulated in breast cancer and correlated with poor survival, and knockdown of PHF5A significantly suppressed cell proliferation, migration, and tumor formation. PHF5A was required for SF3b spliceosome stability and linked the complex to histones, and the PHF5A-SF3b complex modulated AS changes in apoptotic signaling. In addition, expression of a short truncated FAS-activated serine/threonine kinase (FASTK) protein was increased after PHF5A ablation and facilitated Fas-mediated apoptosis. This PHF5A-modulated FASTK-AS axis was widely present in breast cancer specimens, particularly those of the triple-negative subtype. Taken together, our findings reveal that PHF5A serves as an epigenetic suppressor of apoptosis and thus provides a mechanistic basis for breast cancer progression and may be a valuable therapeutic target.Significance: This study provides an epigenetic mechanistic basis for the aggressive biology of breast cancer and identifies a translatable therapeutic target. Cancer Res; 78(12); 3190-206. ©2018 AACR. ©2018 American Association for Cancer Research.