MicroRNA-455-3p promotes invasion and migration in triple negative breast cancer by targeting tumor suppressor EI24

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. The cell cycle regulator cyclin A2 (CCNA2) plays a role in tumor development. Herein, we explored the role of CCNA2 in TNBC. METHODS: We analyzed CCNA2 expression in 15 pairs of TNBC and adjacent tissues and assessed the relationship between CCNA2 expression using the tissue microarray cohort. Furthermore, we used two TNBC cohort datasets to analyze the correlation between CCNA2 and E2F transcription factor 1 (E2F1) and a luciferase reporter to explore their association. Through rescue experiments, we analyzed the effects of E2F1 knockdown on CCNA2 expression and cellular behavior. RESULTS: We found that CCNA2 expression in TNBC was significantly higher than that in adjacent tissues with similar observations in MDA-MB-231 and MDA-MB-468 cells. E2F1 was highly correlated with CCNA2 as observed through bioinformatics analysis (R= 0.80, P< 0.001) and through TNBC tissue verification analysis (R= 0.53, P< 0.001). We determined that E2F1 binds the +677 position within the CCNA2 promoter. Moreover, CCNA2 overexpression increased cell proliferation, invasion, and migration owing to E2F1 upregulation in TNBC. CONCLUSION: Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.

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

Technology in Cancer Research & Treatment ◽

10.1177/1533033820977523 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097752

Author(s):

Lin Gan ◽

Huachao Yang ◽

Zhifeng Xiong ◽

Zailiang Yang ◽

Ting Wang ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Cell Invasion ◽

Therapeutic Target ◽

Triple Negative ◽

Janus Kinase ◽

Potential Therapeutic Target ◽

Invasion And Migration ◽

Over Expression ◽

And Migration

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.

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The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by Promoting Apoptosis, Regulating the MAPK Pathway and Inducing Mitochondrial Dysfunction

International Journal of Molecular Sciences ◽

10.3390/ijms21031038 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1038

Author(s):

Jiajia Zhang ◽

Jiajia Dai ◽

Qingxuan Zheng ◽

Shuju Guo ◽

Yanyan Yu ◽

...

Keyword(s):

Breast Cancer ◽

Mitochondrial Dysfunction ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Mapk Pathway ◽

Invasion And Migration ◽

Aggressive Cancer ◽

Tnbc Cell Line ◽

And Migration

Triple negative breast cancer (TNBC) is the most aggressive cancer in women, and despite improved treatments, it remains a major cause of morbidity and mortality. We and others have demonstrated that different hybrid compounds targeting PARP/MAPK or other pathways to inhibit cancer progression may lead to promising therapeutic results. We introduced fluorine to alter the physical properties of the compounds. TSC-3C was one of the generated compounds. Upon treatment with TSC-3C, MDA-MB-231 cell proliferation, invasion, and migration were inhibited. TSC-3C induced MDA-MB-231 cell mitochondrial dysfunction and apoptosis, which may be caused by reducing the level of phosphorylated p44/42 MAPK (ERK1/2) and increasing the level of p-JNK. The present study may help to elucidate the role of the MAPK pathway in the development of breast cancer and may promote further research on halogenated heterocyclic compounds for the treatment of breast cancer.

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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

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CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition

Pathology & Oncology Research ◽

10.1007/s12253-019-00681-6 ◽

2019 ◽

Vol 26 (2) ◽

pp. 1153-1163 ◽

Cited By ~ 1

Author(s):

Ze-Qiang Ren ◽

Wen-Jing Yan ◽

Xiu-Zhong Zhang ◽

Peng-Bo Zhang ◽

Chong Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration

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Long non‑coding RNA TTN‑AS1 regulates the proliferation, invasion and migration of triple‑negative breast cancer by targeting miR‑211‑5p

Molecular Medicine Reports ◽

10.3892/mmr.2020.11683 ◽

2020 ◽

Vol 23 (1) ◽

pp. 1-1

Author(s):

Erhu Sun ◽

Xiaofeng Liu ◽

Cheng Lu ◽

Kangsheng Liu

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Invasion And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna

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R-Spondin 2 Promoted Proliferation, Invasion and Migration of Triple Negative Breast Cancer Cells Through Activating Wnt/β-Catenin Signaling Pathway After Axin2 Inhibition

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2221 ◽

2020 ◽

Vol 10 (1) ◽

pp. 26-36

Author(s):

XiaoHu Sun ◽

Yue Yu ◽

Jie Ge ◽

Xin Wang ◽

XuChen Cao

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Invasion And Migration ◽

Tnbc Cell ◽

And Migration ◽

Related Proteins

Protein R-spondin 2, which is known as roof plate-specific spondin 2, is an extracellular matrix secreted protein that participates in a wide range of biological processes. However, the expression of R-spondin 2 in triple negative breast cancer (TNBC) and its specific mechanism have not been reported. In this study, RT-qPCR and western blot were used to detect the expression of R-spondin 2 and Axin2 in cells. Cell transfection techniques were used to overexpress Axin2 and interfere with the expression of R-spondin 2. CCk-8 and clone formation assay were used to detect cell viability. Wound healing and Traswell techniques were used to test the rate of invasion and migration of TNBC cells. Western blot was used to detect the expression of related proteins. The results showed that the expression of R-spondin 2 in TNBC cell lines was significantly increased compared with normal breast cancer cells. After interfering with the expression of R-spondin 2 in TNBC cell lines, the rate of cell viability, invasion and migration were decreased. It was also found that the expressions of Axin2 and β-catenin and Cyclin-D1, which are wnt/β-catenin pathway related proteins, were significantly decreased. Subsequently, the overexpression of Axin2 can inhibit the proliferation, invasion and migration that were ever promoted by R-spondin 2 of TNBC cells. Moreover, the overexpression of Axin2 inhibited the activation of wnt/β-catenin signaling pathway, which was also activated by R-spondin 2 in TNBC cells. In a word, R-spondin 2 promoted proliferation, invasion and migration of triple negative breast cancer cells through activating wnt/β-catenin signaling pathway after Axin2 inhibition.

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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.

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