A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1
A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1
复制标题
miRNA-HERC4 通路通过灭活肿瘤抑制因子 LATS1 促进乳腺肿瘤发生
DOI：
10.1007/s13238-019-0607-2
复制
发表时间：
2019-08-01
期刊：
影响因子：
21.1
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Xu, Youqin;Ji, Kaiyuan;Xu, Yang
E3连接酶HERC4在人乳腺癌中过表达，其表达水平与乳腺癌患者预后相关。然而，HERC4在乳腺肿瘤发生中的作用尚不清楚。本研究表明，在人乳腺癌细胞中，HERC4的下调可显著抑制其在体内的增殖、存活、迁移和肿瘤生长，而HERC4的过表达可促进其侵袭性致瘤活性。HERC4是一种新的肿瘤抑制因子LATS1的E3连接酶，通过促进LATS1的泛素化来破坏LATS1的稳定。miRNA-136-5p和miRNA-1285-5p在人乳腺癌中表达降低，与乳腺癌患者预后呈负相关，直接参与抑制HERC4的表达。综上所述，我们发现miRNA-HERC4-LATS1通路在乳腺癌的发病机制中发挥重要作用，代表了人类乳腺癌新的治疗靶点。
AbstractsThe 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 growthin 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.