132 POLQ up-regulation is associated with poor survival in breast cancer, perturbs DNA replication and promotes genetic instability

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

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Syndecan-1 Promotes Angiogenesis in Triple-Negative Breast Cancer through the Prognostically Relevant Tissue Factor Pathway and Additional Angiogenic Routes

Cancers ◽

10.3390/cancers13102318 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2318

Author(s):

Eyyad Nassar ◽

Nourhan Hassan ◽

Eslam A. El-Ghonaimy ◽

Hebatallah Hassan ◽

Mahmoud Salah Abdullah ◽

...

Keyword(s):

Breast Cancer ◽

Tissue Factor ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Network Formation ◽

Umbilical Vein ◽

Poor Survival ◽

Altered Expression ◽

Basal Breast Cancer

Triple-negative breast cancer (TNBC) is characterized by increased angiogenesis, metastasis, and poor survival. Dysregulation of the cell surface heparan sulfate proteoglycan and signaling co-receptor Syndecan-1 is linked to poor prognosis. To study its role in angiogenesis, we silenced Syndecan-1 in TNBC cell lines using a 3D human umbilical vein endothelial cell (HUVEC) co-culture system. Syndecan-1 siRNA depletion in SUM-149, MDA-MB-468, and MDA-MB-231 cells decreased HUVEC tubule network formation. Angiogenesis array revealed reduced VEGF-A and tissue factor (TF) in the Syndecan-1-silenced secretome. qPCR independently confirmed altered expression of F3, F7, F2R/PAR1, F2RL1/PAR2, VEGF-A, EDN1, IGFBP1, and IGFBP2 in SUM-149, MDA-MB-231, and MDA-MB-468 cells. ELISA revealed reduced secreted endothelin-1 (SUM-149, MDA-MB-468) and TF (all cell lines) upon Syndecan-1 depletion, while TF pathway inhibitor treatment impaired angiogenesis. Survival analysis of 3951 patients demonstrated that high expression of F3 and F7 are associated with better relapse-free survival, whereas poor survival was observed in TNBC and p53 mutant basal breast cancer (F3) and in ER-negative and HER2-positive breast cancer (F2R, F2RL1). STRING protein network analysis revealed associations of Syndecan-1 with VEGF-A and IGFBP1, further associated with the TF and ET-1 pathways. Our study suggests that TNBC Syndecan-1 regulates angiogenesis via the TF and additional angiogenic pathways and marks its constituents as novel prognostic markers and therapeutic targets.

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High serum uric acid concentration predicts poor survival in patients with breast cancer

Clinica Chimica Acta ◽

10.1016/j.cca.2017.08.027 ◽

2017 ◽

Vol 473 ◽

pp. 160-165 ◽

Cited By ~ 9

Author(s):

Cai-Feng Yue ◽

Pin-Ning Feng ◽

Zhen-Rong Yao ◽

Xue-Gao Yu ◽

Wen-bin Lin ◽

...

Keyword(s):

Breast Cancer ◽

Uric Acid ◽

Serum Uric Acid ◽

Acid Concentration ◽

High Serum ◽

Uric Acid Concentration ◽

Poor Survival ◽

Serum Uric Acid Concentration

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p85 Protein Expression is Associated with Poor Survival in HER2-Positive Patients with Advanced Breast Cancer Treated with Trastuzumab

Pathology & Oncology Research ◽

10.1007/s12253-014-9818-2 ◽

2014 ◽

Vol 21 (2) ◽

pp. 273-282 ◽

Cited By ~ 6

Author(s):

Kitty Pavlakis ◽

Mattheos Bobos ◽

Anna Batistatou ◽

Vassiliki Kotoula ◽

Anastasia G. Eleftheraki ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

Poor Survival ◽

Her2 Positive

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MiR-940 promotes malignant progression of breast cancer by regulating FOXO3

Bioscience Reports ◽

10.1042/bsr20201337 ◽

2020 ◽

Vol 40 (9) ◽

Author(s):

Huayao Zhang ◽

Jingwen Peng ◽

Jianguo Lai ◽

Haiping Liu ◽

Zhiyuan Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Colony Formation ◽

Target Gene ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Poor Survival ◽

High Level ◽

The Relationship ◽

Proliferation And Invasion

Abstract Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients (P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.

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