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Regulation of ERα-dependent breast cancer metastasis by a miR-29a signaling.

Authors :
Lü, Jinhui
Zhao, Qian
Guo, Yuefan
Li, Danni
Xie, Heying
Liu, Cuicui
Hu, Xin
Liu, Suling
Hou, Zhaoyuan
wei, Xunbin
Zheng, Deyou
Pestell, Richard G.
Yu, Zuoren
Source :
Journal of Experimental & Clinical Cancer Research (17569966). 4/20/2023, Vol. 42 Issue 1, p1-14. 14p.
Publication Year :
2023

Abstract

Malignant breast cancer (BC) remains incurable mainly due to the cancer cell metastasis, which is mostly related to the status of Estrogen receptor alpha (ERα). However, our understanding of the mechanisms through which ERα regulates cancer cell metastasis remains limited. Here we identified a miR-29a-PTEN-AKT axis as a downstream signaling pathway of ERα governing breast cancer progression and metastasis. Two estrogen response element (ERE) half sites were identified in the promoter and enhancer regions of miR-29a, which mediated transcriptional regulation of miR-29a by ERα. Low level of miR-29a showed association with reduced metastasis and better survival in ERα+ luminal subtype of BC. In contrast, high level of miR-29a was detected in ERα- triple negative breast cancer (TNBC) in association with distant metastasis and poor survival. miR-29a overexpression in BC tumors increased the number of circulating tumor cells and promoted lung metastasis in mice. Targeted knockdown of miR-29a in TNBC cells in vitro or administration of a nanotechnology-based anti-miR-29a delivery in TNBC tumor-bearing mice in vivo suppressed cellular invasion, EMT and lung metastasis. PTEN was identified as a direct target of miR-29a, inducing EMT and metastasis via AKT signaling. A small molecular inhibitor of AKT attenuated miR-29a-induced EMT. These findings demonstrate a novel mechanism responsible for ERα-regulated breast cancer metastasis, and reveal the combination of ERα status and miR-29a levels as a new risk indicator in BC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17569966
Volume :
42
Issue :
1
Database :
Academic Search Index
Journal :
Journal of Experimental & Clinical Cancer Research (17569966)
Publication Type :
Academic Journal
Accession number :
163232997
Full Text :
https://doi.org/10.1186/s13046-023-02665-6