miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2

MicroRNAs (miRNAs) are emerging as critical mediators in tumors, including triple-negative breast cancer (TNBC). The role of miR-518a-3p in TNBC was investigated to identify potential therapeutic target. Data from KM Plotter database ( www.kmplot.com ) showed that high miR-518a-3p expression was significantly associated with overall survival of patients with TNBC ( p = 0.04). The expression of miR-518a-3p was dysregulated in TNBC cells. Functional assays revealed that over-expression of miR-518a-3p inhibited cell invasion and migration of TNBC. Additionally, miR-518a-3p could target TMEM2 (transmembrane protein 2), and decreased protein and mRNA expression of TMEM2 in TNBC cells. Knockdown of TMEM2 suppressed cell invasion and migration through inhibiting phospho (p)-JAK1 (Janus kinase 1) and p-STAT (signal transducer and activator of transcription protein) 1/2. Moreover, over-expression of TMEM2 counteracted the suppressive effect of miR-518a-3p on TNBC invasion and migration through promoting the levels of p-JAK1 and p-STAT1/2. In conclusion, miR-518a-3p negatively regulates the JAK/STAT pathway via targeting TMEM2 and suppresses invasion and migration in TNBC, suggesting that miR-518a-3p may be a potential therapeutic target in TNBC.

Download Full-text

BCL11A confers cell invasion and migration in androgen receptor‑positive triple‑negative breast cancer

Oncology Letters ◽

10.3892/ol.2020.11383 ◽

2020 ◽

Cited By ~ 1

Author(s):

Xin Wang ◽

Yumei Xu ◽

Kun Xu ◽

Yajuan Chen ◽

Xiudi Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Triple Negative Breast Cancer ◽

Cell Invasion ◽

Triple Negative ◽

Invasion And Migration ◽

And Migration

Download Full-text

Huaier polysaccharides suppress triple-negative breast cancer metastasis and epithelial-mesenchymal transition by inducing autophagic degradation of Snail

Cell & Bioscience ◽

10.1186/s13578-021-00682-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuan Tian ◽

Jin Wu ◽

Lingjuan Zeng ◽

Linxi Zhou ◽

Ying Hu ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Cell Invasion ◽

Cancer Metastasis ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Inhibitory Effects ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. Results This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. Conclusions This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.

Download Full-text