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MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis
Junchao Cai, … , Jueheng Wu, Mengfeng Li
Junchao Cai, … , Jueheng Wu, Mengfeng Li
Published January 16, 2013
Citation Information: J Clin Invest. 2013;123(2):566-579. https://doi.org/10.1172/JCI65871.
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Research Article Oncology Article has an altmetric score of 12

MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis

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Abstract

Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.

Authors

Junchao Cai, Hongyu Guan, Lishan Fang, Yi Yang, Xun Zhu, Jie Yuan, Jueheng Wu, Mengfeng Li

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Figure 1

miR-374a is markedly overexpressed in metastatic breast cancer cell lines.

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miR-374a is markedly overexpressed in metastatic breast cancer cell line...
(A) miRNA array analysis showed differentially expressed miRNAs in parental MDA-MB-435 cells and their lung metastatic derivatives. Pseudo-color represents intensity scale of metastatic derivatives versus parental cells. (B) Real-time PCR analysis of the expression levels of miR-374a in human breast cancer cell lines compared with primary NBECs and spontaneously immortalized MCF10A cells. Error bars represent mean ± SD from 3 independent experiments. *P < 0.05.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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