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论文题目: Loss of TDP43 Inhibits Progression of Triple-negative Breast Cancer in Coordination with SRSF3
作者: Hao Ke, Limin Zhao, Honglei Zhang, Xu Feng, Haibo Xu, Junjun Hao, Shaowei Wang, Qin Yang, Li Zou, Xiaosan Su, Liqiong Wang, Chunlian Wu, Yang Wang, Jianyun Nie, Baowei Jiao
联系作者: jiaobaowei@mail.kiz.ac.cn
发表年度: 2018
DOI: DOI: 10.1073/pnas.1714573115
摘要:

Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells. Deep sequencing analysis and functional experiments indicate that TDP43 alters most splicing events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific splicing events, including downstream genes PAR3 and NUMB. The effect of reduced metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3 complex and downstream PAR3 isoform are potential therapeutic targets for TNBC

刊物名称: Proceedings of the National Academy of Sciences of the United States of America
论文出处: http://www.pnas.org/content/pnas/early/2018/03/21/1714573115.full.pdf
影响因子: 9.661(2016年)