A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1

doi:10.1007/s13238-019-0607-2

Protein Cell

2019, Vol. 10

Issue (8) : 595-605 https://doi.org/10.1007/s13238-019-0607-2

RESEARCH ARTICLE

A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1

Youqin Xu¹, Kaiyuan Ji¹, Meng Wu¹, Bingtao Hao¹(

), Kai-tai Yao¹(

), Yang Xu^1,²(

)

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

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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

Corresponding Author(s): Bingtao Hao,Kai-tai Yao,Yang Xu

Issue Date: 22 August 2019

Cite this article:

Youqin Xu,Kaiyuan Ji,Meng Wu, et al. A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1[J]. Protein Cell, 2019, 10(8): 595-605.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-019-0607-2
https://academic.hep.com.cn/pac/EN/Y2019/V10/I8/595

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