Kaiyuan Ji
Meng Wu
Bingtao Hao
Kai-tai Yao
Yang Xu
1 Guangdong Provincial Key laboratory of Tumor Immunotherapy, School of Basic Medical Sciences, Cancer Research Institute, Southern Medical University, Guangzhou 510632, China;
2 Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Funds: We thank Xinrui Liu for technical support. This study is supported by National Natural Science Foundation of China (Grant Nos. 81430032 and U1601222), the leading talents of Guangdong Province Program (No. 00201516), and Major basic research developmental project of the Natural Science Foundation of Guangdong Province.
Received Date: 2018-09-11
Rev Recd Date:2018-12-21
Abstract
Abstract
The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4- LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer.Keywords: E3 ligase,
tumorigenesis,
ubiquitination,
tumor suppressor,
miRNA
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